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 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.

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.

Adopting World Health Organization Multimodal Infection Prevention and Control Strategies to Respond to COVID-19, Kenya.

The World Health Organization advocates a multimodal approach to improving infection prevention and control (IPC) measures, which Kenya adopted in response to the COVID-19 pandemic. The Kenya Ministry of Health formed a national IPC committee for policy and technical leadership, coordination, communication, and training. During March-November 2020, a total of 69,892 of 121,500 (57.5%) healthcare workers were trained on IPC. Facility readiness assessments were conducted in 777 health facilities using a standard tool assessing 16 domains. A mean score was calculated for each domain across all facilities. Only 3 domains met the minimum threshold of 80%. The Ministry of Health maintained a national list of all laboratory-confirmed SARS-CoV-2 infections. By December 2020, a total of 3,039 healthcare workers were confirmed to be SARS-CoV-2-positive, an infection rate (56/100,000 workers) 12 times higher than in the general population. Facility assessments and healthcare workers' infection data provided information to guide IPC improvements.

Prevalence of colonization with multidrug-resistant bacteria in communities and hospitals in Kenya.

We estimated the prevalence of extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE), carbapenem-resistant Enterobacterales (CRE), and methicillin-resistant Staphylococcus aureus (MRSA) in communities and hospitals in Kenya to identify human colonization with multidrug-resistant bacteria. Nasal and fecal specimen were collected from inpatients and community residents in Nairobi (urban) and Siaya (rural) counties. Swabs were plated on chromogenic agar to presumptively identify ESCrE, CRE and MRSA isolates. Confirmatory identification and antibiotic susceptibility testing were done using the VITEK®2 instrument. A total of 1999 community residents and 1023 inpatients were enrolled between January 2019 and March 2020. ESCrE colonization was higher in urban than rural communities (52 vs. 45%; P = 0.013) and in urban than rural hospitals (70 vs. 63%; P = 0.032). Overall, ESCrE colonization was ~ 18% higher in hospitals than in corresponding communities. CRE colonization was higher in hospital than community settings (rural: 7 vs. 1%; urban: 17 vs. 1%; with non-overlapping 95% confidence intervals), while MRSA was rarely detected (≤ 3% overall). Human colonization with ESCrE and CRE was common, particularly in hospitals and urban settings. MRSA colonization was uncommon. Evaluation of risk factors and genetic mechanisms of resistance can guide prevention and control efforts tailored to different environments.

Point-prevalence survey of antibiotic use at three public referral hospitals in Kenya.

Antimicrobial stewardship encourages appropriate antibiotic use, the specific activities of which will vary by institutional context. We investigated regional variation in antibiotic use by surveying three regional public hospitals in Kenya. Hospital-level data for antimicrobial stewardship activities, infection prevention and control, and laboratory diagnostic capacities were collected from hospital administrators, heads of infection prevention and control units, and laboratory directors, respectively. Patient-level antibiotic use data were abstracted from medical records using a modified World Health Organization point-prevalence survey form. Altogether, 1,071 consenting patients were surveyed at Kenyatta National Hospital (KNH, n = 579), Coast Provincial General Hospital (CPGH, n = 229) and Moi Teaching and Referral Hospital (MTRH, n = 263). The majority (67%, 722/1071) were ≥18 years and 53% (563/1071) were female. Forty-six percent (46%, 489/1071) were receiving at least one antibiotic. Antibiotic use was higher among children <5 years (70%, 150/224) than among other age groups (40%, 339/847; P < 0.001). Critical care (82%, 14/17 patients) and pediatric wards (59%, 155/265) had the highest proportion of antibiotic users. Amoxicillin/clavulanate was the most frequently used antibiotic at KNH (17%, 64/383 antibiotic doses), and ceftriaxone was most used at CPGH (29%, 55/189) and MTRH (31%, 57/184). Forty-three percent (326/756) of all antibiotic prescriptions had at least one missed dose recorded. Forty-six percent (204/489) of patients on antibiotics had a specific infectious disease diagnosis, of which 18% (37/204) had soft-tissue infections, 17% (35/204) had clinical sepsis, 15% (31/204) had pneumonia, 13% (27/204) had central nervous system infections and 10% (20/204) had obstetric or gynecological infections. Of these, 27% (56/204) had bacterial culture tests ordered, with culture results available for 68% (38/56) of tests. Missed antibiotic doses, low use of specimen cultures to guide therapy, high rates of antibiotic use, particularly in the pediatric and surgical population, and preference for broad-spectrum antibiotics suggest antibiotic use in these tertiary care hospitals is not optimal. Antimicrobial stewardship programs, policies, and guidelines should be tailored to address these areas.

Improving hand hygiene practices in two regional hospitals in Kenya using a continuous quality improvement (CQI) approach.

BACKGROUND: Hand hygiene (HH) is central in prevention of health care-associated infections. In low resource settings, models to improve HH compliance are needed. We implemented a continuous quality improvement (CQI) program targeting HH in two hospitals in Kenya. OBJECTIVE: To determine the impact of the HH CQI program and identify factors associated with HH compliance between 2018 and 2019. METHODS: A CQI project targeting the improvement of hand hygiene was implemented, including training and mentorship. Data were collected monthly between April 2018 and December 2019 in Thika and Kitale Hospitals. Healthcare workers trained on Infection Prevention and Control (IPC) observed and recorded HH opportunities and subsequent compliance among staff, including nurses, clinicians, and auxiliary staff, using the World Health Organization's "My Five Moments for Hand Hygiene" tool. Covariates were explored using mixed-effects logistic regression with random department-level intercepts. RESULTS: Hand hygiene compliance improved from 27% at baseline to 44% after 21 months. Indication/moment for HH was significantly associated with compliance. Adjusting for site, professional category and department, compliance was higher after a moment of body fluid exposure (aOR 1.43, 95% CI 1.17-1.74, p value < 0.001) and lower before an aseptic procedure (aOR 0.12, 95% CI 0.08-0.17, p value < 0.001) compared to after patient contact. Wearing of gloves often replaced proper HH in surgical departments, which although not significant, had lower compliance compared to departments for internal medicine (aOR 0.93, 95% CI 0.85-1.02). Adjusted HH compliance from all quarters improved from baseline, but comparing each quarter to the previous quarter, the improvement fluctuated over time. CONCLUSION: Training and mentorship on the importance of HH for all moments is needed to improve overall HH compliance. CQI with regular monitoring and feedback of HH performance can be an effective approach in improving HH compliance in public hospitals in Kenya.

Exploration of risk factors for ceftriaxone resistance in invasive non-typhoidal Salmonella infections in western Kenya.

Multidrug-resistant non-typhoidal Salmonella (NTS) infection has emerged as a prominent cause of invasive infections in Africa. We investigated the prevalence of ceftriaxone-resistant invasive NTS infections, conducted exploratory analysis of risk factors for resistance, and described antimicrobial use in western Kenya. We conducted a secondary analysis of existing laboratory, epidemiology, and clinical data from three independent projects, a malaria vaccine trial, a central nervous system (CNS) study, and the International Emerging Infections Program morbidity surveillance (surveillance program) during 2009-2014. We calculated odds ratios (OR) with 95% confidence intervals (CI) for ceftriaxone-resistant NTS infections compared with ceftriaxone-susceptible infections. We surveyed hospitals, pharmacies, and animal drug retailers about the availability and use of antimicrobials. In total, 286 invasive NTS infections were identified in the three projects; 43 NTS isolates were ceftriaxone-resistant. The absolute prevalence of ceftriaxone resistance varied among these methodologically diverse projects, with 18% (16/90) of isolates resistant to ceftriaxone in the vaccine trial, 89% (16/18) in the CNS study, and 6% (11/178) in the surveillance program. Invasive ceftriaxone-resistant infections increased over time. Most ceftriaxone-resistant isolates were co-resistant to multiple other antimicrobials. Having an HIV-positive mother (OR = 3.7; CI = 1.2-11.4) and taking trimethoprim-sulfamethoxazole for the current illness (OR = 9.6, CI = 1.2-78.9) were significantly associated with acquiring ceftriaxone-resistant invasive NTS infection. Ceftriaxone and other antibiotics were widely prescribed; multiple issues related to prescription practices and misuse were identified. In summary, ceftriaxone-resistant invasive NTS infection is increasing and limiting treatment options for serious infections. Efforts are ongoing to address the urgent need for improved microbiologic diagnostic capacity and an antimicrobial surveillance system in Kenya.

Salmonella Serotypes: A Novel Measure of Association with Foodborne Transmission.

Most nontyphoidal Salmonella (NTS) illnesses in the United States are thought to be foodborne. However, transmission routes likely vary among the different serotypes. We developed a relative ranking of NTS serotypes according to the strength of their association with foodborne transmission. We used Laboratory-based Enteric Disease Surveillance data to estimate the proportion of infections for each Salmonella serotype reported from 1998 to 2015 and Foodborne Disease Outbreak Surveillance System data to calculate the proportion of foodborne outbreak-associated Salmonella illnesses caused by each serotype. We calculated the ratios of these proportions to create a foodborne relatedness (FBR) measure for each serotype. Of the top 20 serotypes, Saintpaul (2.14), Heidelberg (1.61), and Berta (1.48) had the highest FBR measures; Mississippi (0.01), Bareilly (0.13), and Paratyphi B variant L(+) tartrate(+) (0.20) had the lowest. The FBRs for the three most prevalent serotypes were 1.22 for Enteritidis, 0.77 for Typhimurium, and 1.16 for Newport. This method provides a quantitative approach to estimating the relative differences in the likelihood that an illness caused by a particular serotype was transmitted by food, which may aid in tailoring strategies to prevent Salmonella illnesses and guide future research into serotype-specific source attribution.

Evaluation of Infection Prevention and Control Readiness at Frontline Health Care Facilities in High-Risk Districts Bordering Ebola Virus Disease-Affected Areas in the Democratic Republic of the Congo - Uganda, 2018.

Infection prevention and control (IPC) in health care facilities is essential to protecting patients, visitors, and health care personnel from the spread of infectious diseases, including Ebola virus disease (Ebola). Patients with suspected Ebola are typically referred to specialized Ebola treatment units (ETUs), which have strict isolation and IPC protocols, for testing and treatment (1,2). However, in settings where contact tracing is inadequate, Ebola patients might first seek care at general health care facilities, which often have insufficient IPC capacity (3-6). Before 2014-2016, most Ebola outbreaks occurred in rural or nonurban communities, and the role of health care facilities as amplification points, while recognized, was limited (7,8). In contrast to these earlier outbreaks, the 2014-2016 West Africa Ebola outbreak occurred in densely populated urban areas where access to health care facilities was better, but contact tracing was generally inadequate (8). Patients with unrecognized Ebola who sought care at health care facilities with inadequate IPC initiated multiple chains of transmission, which amplified the epidemic to an extent not seen in previous Ebola outbreaks (3-5,7). Implementation of robust IPC practices in general health care facilities was critical to ending health care-associated transmission (8). In August 2018, when an Ebola outbreak was recognized in the Democratic Republic of the Congo (DRC), neighboring countries began preparing for possible introduction of Ebola, with a focus on IPC. Baseline IPC assessments conducted in frontline health care facilities in high-risk districts in Uganda found IPC gaps in screening, isolation, and notification. Based on findings, additional funds were provided for IPC, a training curriculum was developed, and other corrective actions were taken. Ebola preparedness efforts should include activities to ensure that frontline health care facilities have the IPC capacity to rapidly identify suspected Ebola cases and refer such patients for treatment to protect patients, staff members, and visitors.

Healthcare-Associated Measles After a Nationwide Outbreak in Mongolia.

Measles virus is highly infectious and can spread rapidly where vaccine coverage is low and isolation precautions suboptimal. We describe healthcare-associated measles transmission during the 2015-2016 measles outbreak in Mongolia, describe infection prevention gaps, and outline preventive strategies.

Use of a Diagonal Approach to Health System Strengthening and Measles Elimination after a Large Nationwide Outbreak in Mongolia.

Measles is a highly transmissible infectious disease that causes serious illness and death worldwide. Efforts to eliminate measles through achieving high immunization coverage, well-performing surveillance systems, and rapid and effective outbreak response mechanisms while strategically engaging and strengthening health systems have been termed a diagonal approach. In March 2015, a large nationwide measles epidemic occurred in Mongolia, 1 year after verification of measles elimination in this country. A multidisciplinary team conducted an outbreak investigation that included a broad health system assessment, organized around the Global Health Security Agenda framework of Prevent-Detect-Respond, to provide recommendations for evidence-based interventions to interrupt the epidemic and strengthen the overall health system to prevent future outbreaks of measles and other epidemic-prone infectious threats. This investigation demonstrated the value of evaluating elements of the broader health system in investigating measles outbreaks and the need for using a diagonal approach to achieving sustainable measles elimination.

Fecal carriage of CTX-M ß-lactamase-producing Enterobacteriaceae in nursing homes in the Kinki region of Japan.

The detection rate of CTX-M-type ß-lactamase-producing Enterobacteriaceae in Japan has significantly increased. Nursing homes may be a reservoir of antibiotic-resistant bacteria. Therefore, we determined the prevalence of, and risk factors associated with, fecal carriage of CTX-M-type ß-lactamase-producing Enterobacteriaceae among nursing home residents. A total of 225 stool samples were collected for phenotypic and genotypic identification of extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae. Multivariate analysis was performed to identify the risk factors associated with fecal carriage of CTX-M producers. The prevalence of CTX-M-type ESBL-producing Enterobacteriaceae, as confirmed by phenotypic and genotypic methods, was 19.6% (44 of 225 samples). Escherichia coli was the predominant CTX-M-type ESBL-producing bacterium among these isolates (41 of 44 isolates). Genotyping of bla CTX-M gene-positive isolates showed that 30 (68.2%), 13 (29.5%), and 1 (2.3%) of 44 samples belonged to groups CTX-M-9, CTX-M-1 and CTX-M-2, respectively. Among the CTX-M-type ESBL-producing Enterobacteriaceae found in nursing homes, 95.5% (42 of 44 isolates) were co-resistant to quinolone antibiotics. In multivariate logistic regression analysis, inability to turn over in bed, diabetes, and invasive procedures within the last 2 years were the only variables independently associated with fecal carriage of CTX-M-type ESBL producers. Nursing home residents in Japan exhibit a high prevalence of CTX-M-type ESBL-producing Enterobacteriaceae carriage, with a high level of co-resistance to quinolones.

Prevalence of and risk factors associated with faecal carriage of CTX-M ß-lactamase-producing Enterobacteriaceae in rural Thai communities.

OBJECTIVES: To determine the prevalence of CTX-M ß-lactamase-producing Enterobacteriaceae and to study the risk factors associated with faecal carriage in asymptomatic rural Thai people. METHODS: In all, 417 stool samples were obtained from rural Thai people and screened for extended-spectrum ß-lactamases (ESBLs) using MacConkey agar supplemented with 2 mg/L cefotaxime. Results were confirmed using cefotaxime and ceftazidime with and without clavulanic acid. The bla(CTX-M) genes were identified and genotyped using PCR with bacterial DNA samples. Multivariate analysis was performed to investigate risk factors associated with the faecal carriage of CTX-M producers. RESULTS: The prevalence of CTX-M-type ESBL-producing Enterobacteriaceae was 65.7%. The CTX-M-9 group (60.6%) was dominant, followed by the CTX-M-1 group (38.7%). Most of the bacteria were Escherichia coli (85.4%) and Klebsiella pneumoniae (4.7%). Of a total of 234 E. coli strains, 48.7% belonged to phylogenetic group A, 28.6% to group B1, 15.8% to group D and 6.8% to group B2. Most CTX-M producers were susceptible to carbapenems and amikacin, but resistant to tetracycline and gentamicin. In a multivariate logistic regression model, better education status (OR 2.245; 95% CI 1.297-3.884), history of hospitalization (OR 1.643; 95% CI 1.036-2.603) and the use of antibiotics within the last 3 months (OR 1.883; 95% CI 1.221-2.903) were independently associated with faecal carriage. CONCLUSIONS: Faecal carriage of CTX-M-type ESBL-producing Enterobacteriaceae among asymptomatic individuals in rural Thailand remains alarmingly high, and previous antibiotic use and a history of hospitalization may contribute to its dissemination.

Prevalence of fecal carriage of extended-spectrum ß-lactamase-producing Enterobacteriaceae among healthy adult people in Japan.

In Japan, the prevalence of extended-spectrum ß-lactamase (ESBL) producers in hospital settings has shown an increasing trend. In the present study, we investigated the prevalence of the fecal carriage of ESBL-producing Enterobacteriaceae among healthy adults. Stool samples were collected for the phenotypic and genotypic identification of ESBL-producing Enterobacteriaceae. We found the prevalence of ESBL producers to be 6.4% by phenotypic identification, and 92.9% of them possessed the bla(CTX-M) gene. Among the CTX-M ESBL-producing Enterobacteriaceae, we identified 11 Escherichia coli and 2 Klebsiella pneumonia strains. The findings suggest that the fecal carriage of CTX-M-type ESBL producers by healthy people is rapidly increasing in Japan. This may be one of the causes of the increased spread of ESBL-producing bacteria in hospitals.

Analysis of risk factors for a high prevalence of extended-spectrum {beta}-lactamase-producing Enterobacteriaceae in asymptomatic individuals in rural Thailand.

The prevalence of and risk factors associated with extended-spectrum ß-lactamase (ESBL)-producing micro-organisms have not been well studied in healthy individuals. The aim of this study was to determine this in healthy individuals in Thailand. Stool samples and questionnaires obtained from 445 participants from three provinces in Thailand were analysed. The antimicrobial susceptibility of the isolates was assessed using phenotypic and genotypic methods. PCR analysis was performed to detect and group the bla(CTX-M) genes. The prevalence of CTX-M-type ESBL-producing Enterobacteriaceae in the three provinces was as follows: 29.3 % in Nan (43/147), 29.9 % in Nakhon Si Thammarat (43/144) and 50.6 % in Kanchanaburi (78/154) (P<0.001). Of the 445 samples, 33 (7.4 %), 1 (0.2 %) and 127 (28.5 %) isolates belonged to the bla(CTX-M) gene groups I, III and IV, respectively. Escherichia coli was the predominant member of the Enterobacteriaceae producing CTX-M-type ESBLs (40/43, 39/43 and 70/78 isolates in Nan, Nakhon Si Thammarat and Kanchanaburi, respectively). No statistically significant association was observed between the presence of ESBL-producing bacteria and gender, age, education, food habits or antibiotic usage. However, the provinces that had the highest prevalence of ESBL-producing Enterobacteriaceae also had the highest prevalence of use and purchase of antibiotics without a prescription. Thus, this study revealed that faecal carriage of ESBL-producing Enterobacteriaceae is very high in asymptomatic individuals in Thailand, with some variations among the provinces. This high prevalence may be linked to antibiotic abuse.