Carbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE) poses a public health issue. Rapid detection of CP-CRE colonization is challenging; existing methods are either expensive or time-consuming. We evaluated an immunochromatographic test (ICT) for detecting carbapenemases directly from broth-enriched rectal swabs. One hundred intensive care patients provided 178 pairs of rectal swabs. One swab was tested using the GeneXpert Carba-R PCR assay; the other was inoculated into brain-heart infusion broth. After 4 and 6 h of incubation at 37 degrees C, the broth was tested with the RESIST-5 O.K.N.V.I. ICT for Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-beta-lactamase (NDM), oxacillinase-48 (OXA-48), Verona integron-encoded metallo-beta-lactamase (VIM), and imipenemase (IMP) carbapenemases. Broths were subcultured after overnight incubation, and recovered carbapenem-resistant Enterobacterales isolates were tested using GeneXpert Carba-R PCR. Sensitivity, specificity, and accuracy were calculated in comparison to culture positive for CP-CRE, confirmed by PCR for KPC, NDM, OXA-48, VIM, and IMP. Of the 178 swabs, 60 were culture positive for CP-CRE. After 6 h, the ICT demonstrated a sensitivity of 65%, specificity of 97.5%, and accuracy of 86.8%. Among heavily soiled swabs, sensitivity reached 81.8% for ICT after 6 h, and the specificity was 100%. The mean execution time for carbapenemase detection using ICT was reduced by 60 h compared to culture. The ICT after 6 h incubation offers reduced execution time for detecting CP-CREs. This method may serve as a valuable rapid screening tool, especially in resource-limited settings.IMPORTANCEThe rapid spread of multidrug-resistant bacteria requires innovative solutions for early detection and prevention measures. In this study, we present a simple protocol for the direct detection of carbapenemases in rectal swabs using an immunochromatographic assay. By optimizing the assay conditions, we achieved rapid and high-accuracy identification of five clinically important carbapenemases. This method can broaden access to rapid CP-CRE detection of fecal colonization-even in laboratories with limited resources-enabling the implementation of faster and more effective infection control measures, potentially reducing the spread of resistance.

BACKGROUND: There is limited knowledge on the extent of antimicrobial stewardship program (ASP) implementation in health care facilities (HCFs) in Latin America. METHODS: We performed an evaluation of ASPs in Latin American HCFs from March 2022 to February 2023 using a structured self-assessment survey associated with a scoring system that evaluated leadership support and accountability, resources, antibiotic stewardship actions, education, and antibiotic use (AU) monitoring and reporting. Additionally, we collected monthly AU data (antibiotic consumption and point prevalence surveys) and number of multidrug-resistant infections in medical-surgical intensive care units. Self-assessment scores were correlated with AU through multivariable regression models adjusting for bed size, country of HCF, and incidence of infections (when appropriate). RESULTS: Of the 39 HCFs recruited for the study, all completed the self-assessment, 36 performed the point prevalence survey, and 29 collected antibiotic consumption data. The overall median self-assessment score was 252.5 (IQR, 212.5-285) for a maximum possible score of 335. A high self-assessment score (top quartile) was associated with higher guideline-compliant AU (odds ratio [OR], 8.63; 95% CI, 3.03-24.6; P < .001), higher use of directed therapy (OR, 2.11; 95% CI, 1.41-3.1; P < .001), and less consumption of anti-methicillin-resistant Staphylococcus aureus agents (OR, -8.59; SE = 4.12; P = .037) after adjusting for bed size, country, and incidence of methicillin-resistant S aureus infections. CONCLUSIONS: Higher-level ASP implementation in Latin American HCFs correlated with better compliance with AU guidelines and decreased the use of vancomycin in the intensive care unit, supporting the need to improve resources for ASPs.

BACKGROUND: This study aimed to evaluate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific binding and neutralizing antibody responses in healthcare workers (HCWs) who received coronavirus disease 2019 (COVID-19) vaccines, with or without postvaccination infections. METHODS: We conducted a prospective, observational cohort study of HCW in 2 hospitals in Manaus, Brazil. From 31 March through 31 May 2021, HCWs had nasal swabs collected and questionnaires administered weekly for 4 visits. Nasal swabs were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction (rRT-PCR). Blood specimens were obtained at visits 1 and 4 unless the HCW was found to be infected. If infected, a blood specimen was collected on days 14 and 28 after symptom onset or date of positive specimen, if asymptomatic. COVID-19 vaccination cards, state immunization records, and self-reported history of previous SARS-CoV-2 infection were obtained. Fully vaccinated HCWs who tested SARS-CoV-2 rRT-PCR positive were classified as postvaccination infections. RESULTS: A total of 771 HCWs were enrolled, with 73.7% (568/771) fully vaccinated. Anti-SARS-CoV-2 S1 immunoglobulin G and neutralizing antibody levels showed steep decay within the first 50 days after COVID-19 vaccination. HCWs with prior SARS-CoV-2 infection had slower visible decay after 50 days compared with those without prior infection. We identified 12 postvaccination infections of 16 HCWs who were SARS-CoV-2 rRT-PCR+, including 4 who also reported previous infection. Those positive for SARS-CoV-2 had lower baseline neutralizing antibody levels against Gamma and Delta variants preinfection (median log10 titers [interquartile range]: Gamma, 1.5 [3]; Delta: 0 [0.25]) compared to those who remained rRT-PCR negative (median log10 titers [interquartile range]: Gamma, 3 [2]; Delta, 1 [2]). CONCLUSIONS: Our findings highlight the importance of routine antibody surveillance, targeted boosters, and hybrid immunity in low and middle income countries. Timely booster doses for HCWs and the development of new vaccines against emerging variants can help sustain immunity and prevent workforce shortages, strengthening healthcare resilience in resource-limited settings.

Rapid detection of Carbapenemase-Producing Enterobacterales (CPE) is essential for informing infection prevention and control actions to curb the spread of antimicrobial resistance. Immunochromatographic Tests (ICTs) offer a quick and cost-effective alternative to molecular methods but are typically designed for bacterial isolates rather than direct clinical specimens. We developed a protocol using the O.K.N.V.I. RESIST-5 ICT (Coris Bioconcept, Gembloux, Belgium) to detect KPC, NDM, OXA-48, VIM, and IMP carbapenemases from broth-enriched mock rectal swabs. A total of 35 well-characterized carbapenemase-producing isolates were inoculated into a 10 % stool matrix to create mock swabs. Swabs were incubated in Brain-Heart Infusion (BHI) broth, with and without a 10 μg meropenem disk, at 37 °C for 4 and 6 h. After incubation, broths were centrifuged, and pellets were tested using the ICT. Sensitivity, specificity, and accuracy were calculated for each method (with/without meropenem disk and incubation period). Optimal performance was achieved with swabs incubated in BHI broth without meropenem for 6 h, showing 100 % sensitivity, specificity, and accuracy for all the five enzymes tested. Incubation with meropenem or shorter incubation times resulted in lower sensitivities, with per-enzyme sensitivities ranging from 0 % to 100 %. The developed protocol enables rapid and accurate detection of five common carbapenemases directly from broth-enriched rectal swabs within 6 h. This method offers a practical alternative to culture-based and molecular techniques, potentially enhancing infection control measures through timely identification of CPE.

OBJECTIVE: Increased antibiotic use (AU) has been reported globally during the COVID-19 pandemic despite low rates of bacterial co-infection. We assessed changes in AU during the COVID-19 pandemic in Indonesia and the Philippines. METHODS: We evaluated hospital-wide AU over 36 months in six hospitals, 3 in Indonesia and 3 in the Philippines. Intravenous antibiotics commonly used for respiratory conditions were selected and grouped for analysis. AU rates were calculated as monthly defined daily dose per 1000 patient-days or patient discharges. Median AU rates were compared from the pre-pandemic (March 2018-February 2020) and pandemic periods (March 2020-February 2021) using quantile regression to assess for statistical significance. Changes in AU during the COVID-19 pandemic were analyzed using interrupted time series analysis. RESULTS: Significant increases were noted in the median AU rate from the pre-pandemic to pandemic period of all antibiotics combined in 3/6 hospitals (percentage change, Δ, 12.5%-63.6%) and anti-pseudomonal antibiotics in 3/6 hospitals (Δ 51.5%-161.5%). In the interrupted time series analysis, an immediate increase (range: 125.40-1762) in the use of all included antibiotics combined was observed in 3/6 hospitals at the onset of the COVID-19 pandemic. One of these 3 hospitals experienced a statistically significant sustained increase, while another experienced a decrease over time. CONCLUSIONS: We observed significant increases in facility-wide inpatient AU during the COVID-19 pandemic in our participating hospitals in Indonesia and the Philippines. These findings reinforce the importance of antibiotic stewardship practices to optimize AU, especially during infectious disease pandemics.

International guidelines are available for the assessment and improvement of antimicrobial stewardship (AMS) programmes: an important strategy to address the escalating global antimicrobial resistance problem. However, existing AMS assessment tools lack contextual specificity for resource-limited settings, leading to limited applicability in Asia. This project aimed to identify relevant themes from current guidance documents to help develop a context-specific assessment tool that can be applied by healthcare facilities (HCFs) to improve local implementation.We performed a sequential approach of a scoping review to identify relevant assessment themes for Asia and an expert survey for getting feedback on the relevance of assessment stems developed from the scoping review. We reviewed English-language published documents discussing AMS implementation or assessment at HCFs globally and in Asia. Themes were derived through content analysis and classified following the predefined context dimensions to develop assessment stems, defined as containing one identified determinant that may influence implementation outcomes. The survey consisting of identified assessment stems was reviewed by 20 locally identified experts in Asia who rated the level of relevance of these stems in AMS implementation in the region.National leadership, training and technical support, and policy and guidance were the most commonly identified themes among 100 themes identified from 73 reviewed documents. From these themes, we developed 131 assessment stems for the expert survey. Of the 131 assessment stems, 117 (89%) were considered relevant for AMS implementation in Asia by at least 80% of respondents. These stems were included in the process of developing a global AMS assessment tool to support HCFs to improve their programmes.In conclusion, national leadership and support represent a distinct and important aspect affecting AMS implementation in HCFs in Asia. The identified assessment themes have substantial value for the formulation of locally relevant implementation strategies tailored to the Asian context.

BACKGROUND: Streptococcus pneumoniae is an important cause of pneumonia, sepsis, and meningitis, which are leading causes of child mortality. Pneumococcal conjugate vaccines (PCVs) protect against disease and nasopharyngeal colonization with vaccine serotypes, reducing transmission to and among unvaccinated individuals. Mozambique introduced 10-valent PCV (PCV10) in 2013. In 2017-2019, 13-valent PCV (PCV13) replaced PCV10, and in September 2019 the schedule changed from three primary doses to two primary doses and a booster; the booster-containing schedule may increase indirect effects. We examined pneumococcal carriage in Mozambique to establish a baseline for estimating the impact of policy changes and to estimate the long-term impact of PCV10 in children aged <5 years. METHODS: We calculated prevalence of carriage of PCV10 serotypes and the 3 additional PCV13 serotypes ('PCV13-unique') among children aged <5 years and their household members in southern Mozambique, between October 2018 and July 2019. Nasopharyngeal swabs were cultured, and isolates underwent Quellung serotyping. For children, we compared these "long-term post-PCV10" data with prior surveys ("pre-PCV" (2012-2013) and "post-PCV10" (2015-2016)) that used the same methods. RESULTS: In 2018-2019, among 1319 children aged under five years, 1064 (80.7 %) were colonized with pneumococcus, among 614 children aged 5- < 18 years, 355 (57.8 %) were colonized, and among 804 adults (aged ≥18 years), 285 (35.4 %) were colonized. The most frequently observed serotypes were 19 A (n = 154, 8.5 % of isolates) and 6 A (n = 107, 5.9 %), both PCV13-unique serotypes. Overall carriage prevalence among children under five years remained stable at approximately 80 % across the carriage studies conducted between 2012 and 2019; between 2015 and 2016 and 2018-2019, the prevalence of PCV10-type carriage declined from 17.7 % to 10.1 %. CONCLUSIONS: Despite substantial declines in PCV10-type carriage initially following vaccine introduction, the continued circulation of PCV10 serotypes and relative high prevalence of PCV13-unique serotypes underscore the need to understand the impact of policy changes on pneumococcus transmission.

BACKGROUND: The objective of this study was to identify antibiotic stewardship (AS) opportunities in Latin American medical-surgical intensive care units (MS-ICUs) and general wards (Gral-wards). METHODS: We conducted serial cross-sectional point prevalence surveys in MS-ICUs and Gral-wards in 41 Latin American hospitals between March 2022 and February 2023. Patients >18 years of age in the units of interest were evaluated for antimicrobial use (AU) monthly (MS-ICUs) or quarterly (Gral-wards). Antimicrobial data were collected using a standardized form by the local AS teams and submitted to the coordinating team for analysis. RESULTS: We evaluated AU in 5780 MS-ICU and 7726 Gral-ward patients. The hospitals' median bed size (interquartile range) was 179 (125-330), and 52% were nonprofit. The aggregate AU prevalence was 53.5% in MS-ICUs and 25.5% in Gral-wards. Most (88%) antimicrobials were prescribed to treat infections, 7% for surgical prophylaxis and 5% for medical prophylaxis. Health care-associated infections led to 63% of MS-ICU and 38% of Gral-ward AU. Carbapenems, piperacillin-tazobactam, intravenous (IV) vancomycin, and ampicillin-sulbactam represented 50% of all AU to treat infections. A minority of IV vancomycin targeted therapy was associated with documented methicillin-resistant Staphylococcus aureus infection or therapeutic drug monitoring. In both units, 17% of antibiotics prescribed as targeted therapy represented de-escalation, while 24% and 15% in MS-ICUs and Gral-wards, respectively, represented an escalation of therapy. In Gral-wards, 32% of antibiotics were used without a microbiologic culture ordered. Half of surgical prophylaxis antibiotics were prescribed after the first 24 hours. CONCLUSIONS: Based on this cohort, areas to improve AU in Latin American hospitals include antibiotic selection, de-escalation, duration of therapy, and dosing strategies.

BACKGROUND: Streptococcus pneumoniae (S. pneumoniae), Haemophilus influenzae (H. influenzae), and Neisseria meningitidis (N. meningitidis) are leading causes of childhood bacterial meningitis and preventable by vaccines. The aim of this hospital-based sentinel surveillance is to describe the epidemiological characteristics of pneumococcal meningitis, including disease burden, and to provide baseline data on pneumococcal serotype distribution to support decision making for pneumococcal conjugate vaccine (PCV) introduction in Vietnam. METHODS: Surveillance for probable bacterial meningitis in children 1-59 months of age is conducted in three tertiary level pediatric hospitals: one in Hanoi and two in Ho Chi Minh City. Cerebrospinal fluid (CSF) specimens were collected via lumbar puncture from children with suspected meningitis. Specimens were transferred immediately to the laboratory department of the respective hospital for cytology, biochemistry, and microbiology testing, including culture. PCR testing was conducted on CSF specimens for bacterial detection (S. pneumoniae, H. influenzae, and N. meningitidis) and pneumococcal serotyping. RESULTS: During 2015-2018, a total of 1,803 children with probable bacterial meningitis were detected; 1,780 had CSF specimens available for testing. Of 245 laboratory-confirmed positive cases, the majority were caused by S. pneumoniae (229,93.5%). Of those with S. pneumoniae detected, over 70% were caused by serotypes included in currently available PCV products; serotypes 6 A/6B (27.1%), 14 (19.7%), and 23 F (16.2%) were the most common serotypes. Children with laboratory-confirmed pneumococcal meningitis were more likely to live in Hanoi (p < 0.0001) and children 12-23 months of age were at greater odds (OR = 1.65, 95% CI: 1.11, 2.43; p = 0.006) of having confirmed pneumococcal meningitis compared to children < 12 months of age when compared to those without laboratory-confirmed bacterial meningitis. Additionally, children with confirmed pneumococcal meningitis were more likely to exhibit signs and symptoms consistent with clinical meningitis compared to negative laboratory-confirmed meningitis cases (p < 0.0001) and had a greater odds of death (OR = 6.18, 95% CI: 2.98, 12.86; p < 0.0001). CONCLUSIONS: Pneumococcal meningitis contributes to a large burden of bacterial meningitis in Vietnamese children. A large proportion are caused by serotypes covered by PCVs currently available. Introduction of PCV into the routine immunization program could reduce the burden of pneumococcal meningitis in Viet Nam.

BACKGROUND: Kenya introduced Synflorix™ (GlaxoSmithKline, PCV10-GSK), a 10-valent pneumococcal conjugate vaccine, in 2011, using three primary doses and, in select areas, catch-up campaigns. Surveys conducted 1-2 years post-introduction showed a stable prevalence of pneumococcal colonization, with declines in vaccine-type carriage. However, little is known about the long-term impact of PCV10-GSK in Kenya. METHODS: We conducted a cross-sectional survey of pneumococcal carriage among children aged <5 years in November-December 2017 in Kibera (Nairobi informal settlement, no catch-up) and Asembo (rural western Kenya, 2-dose catch-up for children 1-4 years), using the same methods and settings as prior annual surveys from 2009 to 2013. Participants were randomly selected from an ongoing population-based surveillance platform. Nasopharyngeal swabs were frozen in skim milk-tryptone-glucose-glycerin media within 4 h and underwent culture with broth enrichment for pneumococcus. Isolates were serotyped by polymerase chain reaction and Quellung. RESULTS: We enrolled 504 children, including 252 from each site; >90 % of participants had received 3 doses of PCV10-GSK. Pneumococcal colonization was detected in 210 (83.3 %) participants in Kibera and 149 (59.1 %) in Asembo, which was significantly lower than the prevalence observed in 2013 (92.9 % and 85.7 %, respectively). PCV10-GSK serotypes were detected in 35/252 (13.9 %) participants in Kibera and 23/252 (9.1 %) in Asembo, respectively; these prevalences were lower, but not statistically different, from vaccine-type carriage prevalences in 2013 (17.3 % and 13.3 %, respectively). In 2017 in both sites, serotypes 3, 6A, 19A, 19F, and 35B were among the most common serotypes. CONCLUSION: Six years post-PCV10-GSK introduction, the prevalence of pneumococcal carriage among children has decreased, and the impact of PCV10-GSK on vaccine-type carriage has plateaued. Kenya recently changed from PCV10-GSK to Pneumosil™ (Serum Institute of India), a 10-valent PCV that includes serotypes 6A and 19A; these data provide historical context for interpreting changes in vaccine-type carriage following the PCV formulation switch.

BACKGROUND: The burden of antimicrobial resistance (AMR) in Latin America is high. Little is known about healthcare workers' (HCWs) knowledge, attitudes, and perceptions of antimicrobial stewardship (AS), AMR, and antibiotic use (AU) in the region. METHODS: HCWs from 42 hospitals from 5 Latin American countries were invited to take an electronic, voluntary, anonymous survey regarding knowledge, attitudes, and perceptions of AS, AMR, and AU between March-April 2023. FINDINGS: Overall, 996 HCWs completed the survey (52% physicians, 32% nurses, 11% pharmacists, 3% microbiologists, and 2% "other"). More than 90% of respondents indicated optimizing AU was a priority at their healthcare facility (HCF), 69% stated the importance of AS was communicated at their HCF, and 23% were unfamiliar with the term "antibiotic stewardship". Most (> 95%) respondents acknowledged that appropriate AU can reduce AMR; however, few thought AU (< 30%) or AMR (< 50%) were a problem in their HCF. Lack of access to antibiogram and to locally endorsed guidelines was reported by 51% and 34% of HCWs, respectively. Among prescribers, 53% did not consider non-physicians' opinions to make antibiotic-related decisions, 22% reported not receiving education on how to select antibiotics based on culture results and 60% stated patients and families influence their antibiotic decisions. CONCLUSIONS: Although HCWs perceived improving AU as a priority, they did not perceive AU or AMR as a problem in their HCF. AS opportunities include improved access to guidelines, access to AMR/AU data, teamwork, and education on AS for HCWs and patients and families.

Background: The burden of antimicrobial resistance (AMR) in Latin America is high. Little is known about healthcare workers’ (HCWs) perceptions of antimicrobial stewardship (AS) and antibiotic use (AU) in the region. Methods: HCWs from 42 hospitals in Panama, Guatemala, Colombia, Ecuador, and Argentina were invited to participate in an electronic, voluntary, anonymous survey regarding perceptions of AS and AU from March-April 2023. All participants were asked 21 questions; prescribers were asked additional questions about antibiotic prescribing. Answers with 5-point Likert scale were categorized into two groups, strongly agree/agree and neutral/disagree/strongly disagree. Results: Of 475 HCWs that completed the survey, 52% were physicians (29% in training), 28% nurses, 13% pharmacists, 3% microbiologists, and 3% “other.” Median years of experience was 12 (interquartile range 6, 20). Although 93% indicated optimizing AU was a priority at their healthcare facility (HCF), only 69% said the importance of AS was communicated at their HCF. Nurses and those in “other” roles were more likely to report lack of familiarity with the term AS than physicians (32% and 27% respectively vs. 21%, P< 0.01).Most (99%) respondents acknowledged that appropriate AU can reduce AMR and that inappropriate AU could harm patients. However, fewer thought antibiotics were overused (30%) or AMR was a problem (52%) in their HCF. Thirty-eight percent of HCWs did not have access to guidelines and 24% did not value recommendations by the AS team (Figure 1). Of prescribers, 99% reported to modify antibiotics based on culture results, 55% do not consult non-physician staff (e.g., pharmacists, nurses) to make antibiotic decisions, 20% do not use local guidelines or do not receive training on how to interpret culture results to make antibiotic decisions (Figure 2). Prescribers felt pressure from colleagues (38%) and patients or their families (63%) to make antibiotic decisions. Conclusion: Although most HCWs perceived improving AU as a priority, they did not perceive AU or AMR to be a problem in their HCF. Opportunities to optimize AU include improved access and adherence to guidelines, access to AMR data, teamwork, and education on AS for HCW. Disclosures: Sara E. Cosgrove, MD, MS, Debiopharm: Advisor/Consultant|Duke Clinical Research Institute: Advisor/Consultant Payal K. Patel, MD MPH, qiagen: Honoraria

Antimicrobial resistance remains a significant global public health threat. Although development of novel antibiotics can be challenging, several new antibiotics with improved activity against multidrug-resistant Gram-negative organisms have recently been commercialised. Expanding access to these antibiotics is a global public health priority that should be coupled with improving access to quality diagnostics, health care with adequately trained professionals, and functional antimicrobial stewardship programmes. This comprehensive approach is essential to ensure responsible use of these new antibiotics.

In “Pneumococcal Meningitis Outbreaks in Africa, 2000–2018: | Systematic Literature Review and Meningitis Surveillance | Database Analyses” by Franklin et al reference #27 was incorrect but is now updated. | We have added the middle initial to the name of author, Jason | M. Mwenda.

The variant of concern (VOC) P.1 emerged in the Amazonas state (Brazil) in November-2020. It contains a constellation of mutations, ten of them in the spike protein. Consequences of these specific mutations at the population level have been little studied so far, despite the detection of P.1 variant in 26 countries, with local transmission in at least four other countries in the Americas and Europe. Here, we estimate P.1’s transmissibility and reinfection using a model-based approach, by fitting data from the Brazilian national health surveillance of hospitalized individuals and frequency of the P.1 variant in Manaus from December 2020 to February 2021, when the city was devastated by four times more cases than in the previous peak (April 2020). The new variant was found to be about 2.6 times more transmissible (95% Confidence Interval (CI): 2.4–2.8) than previous circulating variant(s). The city already had a high prevalence of individuals previously affected by the SARS-CoV-2 virus (estimated as 78%, CI:73–83%), and the fitted model attributed 28% of the cases during the period to reinfections by the variant P.1. Our estimates rank P.1 as the most transmissible among the current identified SARS-CoV-2 VOCs, posing a serious threat and requiring urgent measures to control its global spread.Competing Interest StatementThe authors have declared no competing interest.Clinical TrialEthics approval was not necessary because this study analysed only publicly available data, not including identifiable information.Funding StatementThis work was supported by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brazil (Finance Code 001 to FMDM, LSF and TPP), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Brazil (grant number: 315854/2020-0 to MEB, 141698/2018-7 to RLPS, 313055/2020-3 to PIP, 312559/2020-8 to MASMV, 311832/2017-2 to RAK, 305703/2019-6 to AAMS) and Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, Brazil (grant number: 2019/26310-2 and 2017/26770-8 to CF, 2018/26512-1 to OC, 2018/24037-4 to SPL and contract number: 2016/01343-7 to RAK). Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Ethics approval was not necessary because this study analysed only publicly available data, not including identifiable information.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data used are publicly available. The data sources are described in the manuscript and in supplementary file.

In February 2021, Peru launched a vaccination campaign among healthcare personnel using BBIBP-CorV inactivated whole virus (BBIBP-CorV) COVID-19 vaccine. Two doses of BBIBP-CorV vaccine are recommended, 21 days apart. Data on BBIBP-CorV vaccine effectiveness will inform the use and acceptance of vaccination with BBIBP-CorV vaccine. We evaluated BBIBP-CorV vaccine effectiveness among an existing multi-year influenza cohort at two hospitals in Lima. We analyzed data on 290 participants followed between February and May 2021. Participants completed a baseline questionnaire and provided weekly self-collected anterior nasal swabs tested for SARS-CoV-2 by rRT-PCR for sixteen weeks. We performed multivariable logistic regression models adjusting for pre-selected characteristics (age, sex, exposure to COVID-19 patients, work in intensive care unit or emergency department, BMI, and exposure time in days). BBIBP-CorV vaccine effectiveness was calculated after the two-week post-vaccination period as (1-Odds Ratio for testing SARS-CoV-2 positive)x100%. SARS-CoV-2 was detected by rRT-PCR among 25 (9%) participants during follow-up (February-May 2021). Follow-up period ranged 1-11 weeks (median: 2 weeks). Among cohort participants who were fully vaccinated the adjusted vaccine effectiveness against SARS-CoV-2 infection was estimated as 95% (95% CI: 70%, 99%) and 100% (95% CI: 88%, 100%) for those partially vaccinated. During the study period, vaccination of healthcare personnel with BBIBP-CorV vaccine was effective at reducing SARS-CoV-2 infections in the weeks immediately following vaccination. This information can be used to support vaccination efforts in the region, especially among those who could be concerned about their effectiveness. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

BACKGROUND: The impact of coronavirus disease 2019 (COVID-19) on antimicrobial use (AU) and resistance has not been well evaluated in South America. These data are critical to inform national policies and clinical care. METHODS: At a tertiary hospital in Santiago, Chile, between 2018 and 2022, subdivided into pre- (3/2018-2/2020) and post-COVID-19 onset (3/2020-2/2022), we evaluated intravenous AU and frequency of carbapenem-resistant Enterobacterales (CRE). We grouped monthly AU (defined daily doses [DDD]/1000 patient-days) into broad-spectrum β-lactams, carbapenems, and colistin and used interrupted time-series analysis to compare AU during pre- and post-pandemic onset. We studied the frequency of carbapenemase-producing (CP) CRE and performed whole-genome sequencing analyses of all carbapenem-resistant (CR) Klebsiella pneumoniae (CRKpn) isolates collected during the study period. RESULTS: Compared with pre-pandemic, AU (DDD/1000 patient-days) significantly increased after the pandemic onset, from 78.1 to 142.5 (P < .001), 50.9 to 110.1 (P < .001), and 4.1 to 13.3 (P < .001) for broad-spectrum β-lactams, carbapenems, and colistin, respectively. The frequency of CP-CRE increased from 12.8% pre-COVID-19 to 51.9% after pandemic onset (P < .001). The most frequent CRE species in both periods was CRKpn (79.5% and 76.5%, respectively). The expansion of CP-CRE harboring blaNDM was particularly noticeable, increasing from 40% (n = 4/10) before to 73.6% (n = 39/53) after pandemic onset (P < .001). Our phylogenomic analyses revealed the emergence of two distinct genomic lineages of CP-CRKpn: ST45, harboring blaNDM, and ST1161, which carried blaKPC. CONCLUSIONS: AU and the frequency of CP-CRE increased after COVID-19 onset. The increase in CP-CRKpn was driven by the emergence of novel genomic lineages. Our observations highlight the need to strengthen infection prevention and control and antimicrobial stewardship efforts.

BACKGROUND: Antimicrobial resistance has worsened in Latin America. There is an urgent need to understand the development of antimicrobial stewardship programs (ASPs) and the barriers to implementing effective ASPs in light of limited national action plans or policies to promote ASPs in the region. METHODS: We performed a descriptive mixed-methods study of ASPs in 5 Latin American countries in March-July 2022. An electronic questionnaire with an associated scoring system (hospital ASP self-assessment) was used, and ASP development was classified based on the scores (inadequate, 0-25; basic, 26-50; intermediate, 51-75; or advanced, 76-100). Interviews among healthcare workers (HCWs) involved in antimicrobial stewardship (AS) inquired about behavioral and organizational factors that influence AS activities. Interview data were coded into themes. Results from the ASP self-assessment and interviews were integrated to create an explanatory framework. RESULTS: Twenty hospitals completed the self-assessment, and 46 AS stakeholders from these hospitals were interviewed. ASP development was inadequate/basic in 35% of hospitals, intermediate in 50%, and advanced in 15%. For-profit hospitals had higher scores than not-for-profit hospitals. Interview data validated the self-assessment findings and provided further insight into ASP implementation challenges, which included limited formal hospital leadership support, inadequate staffing and tools to perform AS work more efficiently, limited awareness of AS principles by HCWs, and limited training opportunities. CONCLUSIONS: We identified several barriers to ASP development in Latin America, suggesting the need to create accurate business cases for ASPs to obtain the necessary funding for their effective implementation and sustainability.

The discovery of penicillin in 1928 and its initial use in the 1940s to treat serious infections marked a turning point in modern medicine saving millions of lives [1]. However, antibiotic resistance (AR) has long threatened the advances of modern medicine. Widespread use of penicillin in clinical therapy started in 1943, and a decade later penicillin resistance had already become a major clinical problem [2]. This same phenomenon has been seen with each new antibiotic that has been approved for clinical use. A landmark study recently published showed that in 2019 AR killed more people than any other infectious diseases including human immunodeficiency virus (HIV) and malaria [3]. One in 8 deaths globally are linked to bacterial infections, the second leading cause of death after ischemic heart disease

BACKGROUND: High rates of antibiotic use (AU) among inpatients with coronavirus disease 2019 (COVID-19) despite low rates of bacterial coinfection and secondary infection have been reported. We evaluated the impact of the COVID-19 pandemic on AU in healthcare facilities (HCFs) in South America. METHODS: We conducted an ecologic evaluation of AU in inpatient adult acute care wards in 2 HCFs each in Argentina, Brazil, and Chile. The AU rates for intravenous antibiotics were calculated as the defined daily dose per 1000 patient-days, using pharmacy dispensing records and hospitalization data from March 2018-February 2020 (prepandemic) and March 2020-February 2021 (pandemic). Differences in median AU were compared between the prepandemic and pandemic periods, using the Wilcoxon rank sum test to determine significance. Interrupted time series analysis was used to analyze changes in AU during the COVID-19 pandemic. RESULTS: Compared with the prepandemic period, the median difference in AU rates for all antibiotics combined increased in 4 of 6 HCFs (percentage change, 6.7%-35.1%; P < .05). In the interrupted time series models, 5 of 6 HCFs had significant increases in use of all antibiotics combined immediately at the onset of the pandemic (immediate effect estimate range, 15.4-268), but only 1 of these 5 HCFs experienced a sustained increase over time (change in slope, +8.13; P < .01). The effect of the pandemic onset varied by antibiotic group and HCF. CONCLUSIONS: Substantial increases in AU were observed at the beginning of the COVID-19 pandemic, suggesting the need to maintain or strengthen antibiotic stewardship activities as part of pandemic or emergency HCF responses.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic may have impacted outpatient antibiotic prescribing in low- and middle-income countries such as Brazil. However, outpatient antibiotic prescribing in Brazil, particularly at the prescription level, is not well-described. METHODS: We used the IQVIA MIDAS database to characterize changes in prescribing rates of antibiotics commonly prescribed for respiratory infections (azithromycin, amoxicillin-clavulanate, levofloxacin/moxifloxacin, cephalexin, and ceftriaxone) among adults in Brazil overall and stratified by age and sex, comparing prepandemic (January 2019-March 2020) and pandemic periods (April 2020-December 2021) using uni- and multivariate Poisson regression models. The most common prescribing provider specialties for these antibiotics were also identified. RESULTS: In the pandemic period compared to the prepandemic period, outpatient azithromycin prescribing rates increased across all age-sex groups (incidence rate ratio [IRR] range, 1.474-3.619), with the greatest increase observed in males aged 65-74 years; meanwhile, prescribing rates for amoxicillin-clavulanate and respiratory fluoroquinolones mostly decreased, and changes in cephalosporin prescribing rates varied across age-sex groups (IRR range, 0.134-1.910). For all antibiotics, the interaction of age and sex with the pandemic in multivariable models was an independent predictor of prescribing changes comparing the pandemic versus prepandemic periods. General practitioners and gynecologists accounted for the majority of increases in azithromycin and ceftriaxone prescribing during the pandemic period. CONCLUSIONS: Substantial increases in outpatient prescribing rates for azithromycin and ceftriaxone were observed in Brazil during the pandemic with prescribing rates being disproportionally different by age and sex. General practitioners and gynecologists were the most common prescribers of azithromycin and ceftriaxone during the pandemic, identifying them as potential specialties for antimicrobial stewardship interventions.

BACKGROUND: The SARS-CoV-2 variant of concern (VOC) P.1 (Gamma variant) emerged in the Amazonas State, Brazil, in November 2020. The epidemiological consequences of its mutations have not been widely studied, despite detection of P.1 in 36 countries, with local transmission in at least 5 countries. A range of mutations are seen in P.1, ten of them in the spike protein. It shares mutations with VOCs previously detected in the United Kingdom (B.1.1.7, Alpha variant) and South Africa (B.1.351, Beta variant). METHODS: We estimated the transmissibility and reinfection of P.1 using a model-based approach, fitting data from the national health surveillance of hospitalized individuals and frequency of the P.1 variant in Manaus from December-2020 to February-2021. RESULTS: Here we estimate that the new variant is about 2.6 times more transmissible (95% Confidence Interval: 2.4-2.8) than previous circulating variant(s). Manaus already had a high prevalence of individuals previously affected by the SARS-CoV-2 virus and our fitted model attributed 28% of Manaus cases in the period to reinfections by P.1, confirming the importance of reinfection by this variant. This value is in line with estimates from blood donors samples in Manaus city. CONCLUSIONS: Our estimates rank P.1 as one of the most transmissible among the SARS-CoV-2 VOCs currently identified, and potentially as transmissible as the posteriorly detected VOC B.1.617.2 (Delta variant), posing a serious threat and requiring measures to control its global spread.

Streptococcus pneumoniae is a cause of invasive diseases such as pneumonia, meningitis, and other serious infections among children and adults in Paraguay. This study was conducted to establish S. pneumoniae baseline prevalence, serotype distribution, and antibiotic resistance patterns in healthy children aged 2 to 59 months and adults ≥60 years of age prior to the introduction of PCV10 in the national childhood immunization program in Paraguay. Between April and July 2012, a total of 1444 nasopharyngeal swabs were collected, 718 from children aged 2 to 59 months and 726 from adults ≥60 years of age. The pneumococcal isolation, serotyping, and antibiotic susceptibility testing were performed using standard tests. Pneumococcal colonization prevalence was 34.1% (245/718) in children and 3.3% (24/726) in adults. The most frequent pneumococcal vaccine-types (VT) detected in the children were 6B (42/245), 19F (32/245), 14 (17/245), and 23F (20/245). Carriage prevalence with PCV10 serotypes was 50.6% (124/245) and PCV13 was 59.5% (146/245). Among colonized adults, prevalence of PCV10 and PCV13 serotypes were 29.1% (7/24) and 41.6% (10/24), respectively. Colonized children were more likely to share a bedroom, have a history of respiratory infection or pneumococcal infection compared to non-colonized children. no associations were found in adults. However, no significant associations were found in children and neither in adults. Vaccine-type pneumococcal colonization was highly prevalent in children and rare in adults in Paraguay prior to vaccine introduction, supporting the introduction of PCV10 in the country in 2012. These data will be useful to evaluate the impact of PCV introduction in the country.

In February 2021, Peru launched a COVID-19 vaccination campaign among healthcare personnel using an inactivated whole-virus vaccine. The manufacturer recommended 2 vaccine doses 21 days apart. We evaluated vaccine effectiveness among an existing multiyear influenza vaccine cohort at 2 hospitals in Lima. We analyzed data on 290 participants followed during February-May 2021. Participants completed a baseline questionnaire and provided weekly self-collected nasal swab samples; samples were tested by real-time reverse transcription PCR. Median participant follow-up was 2 (range 1-11) weeks. We performed multivariable logistic regression and adjusted for preselected characteristics. During the study, 25 (9%) participants tested SARS-CoV-2-positive. We estimated adjusted vaccine effectiveness at 95% (95% CI 70%-99%) among fully vaccinated participants and 100% (95% CI 88%-100%) among partially vaccinated participants. These data can inform the use and acceptance of inactivated whole-virus vaccine and support vaccination efforts in the region.

IMPORTANCE: The association of 13-valent pneumococcal conjugate vaccine (PCV13) use with pneumonia hospitalization in older adults, especially those with underlying medical conditions, is not well described. OBJECTIVE: To evaluate the association of PCV13 use with pneumonia, non-health care-associated (non-HA) pneumonia, and lobar pneumonia (LP) hospitalization among US Medicare beneficiaries 65 years or older. DESIGN, SETTING, AND PARTICIPANTS: This cohort study with time-varying exposure assignment analyzed claims data from US Medicare beneficiaries 65 years or older enrolled in Parts A/B with a residence in the 50 US states or the District of Columbia by September 1, 2014. New Medicare Parts A/B beneficiaries within 6 months after their 65th birthday were continuously included in the cohort after September 1, 2014, and followed through December 31, 2017. Participants were censored if they died, changed enrollment status, or developed a study outcome. Most of the analyses were conducted from 2018 to 2019, and additional analyses were performed from 2021 to 2022. EXPOSURES: Use of PCV13 vaccination 14 days or more before pneumonia hospitalization. MAIN OUTCOMES AND MEASURES: Discrete-time survival models were used to estimate the incidence rate ratio (IRR) and number of pneumonia hospitalizations averted through PCV13 use. The adjusted IRR for the association of PCV13 vaccination with pneumonia hospitalization was used to estimate vaccine effectiveness (VE). RESULTS: At the end of follow-up (December 2017), 24121625 beneficiaries (13593975 women [56.4%]; 418005 [1.7%] Asian, 1750807 [4.8%] Black, 338044 [1.4%] Hispanic, 111508 [0.5%] Native American, and 20700948 [85.8%] White individuals) were in the cohort; 4936185 (20.5%) had received PCV13 only, and 10646220 (79.5%) had not received any pneumococcal vaccines. More than half of the beneficiaries in the cohort were younger than 75 years, White, and had either immunocompromising or chronic medical conditions. Coverage with PCV13 increased from 0.8% (September 2014) to 41.5% (December 2017). The VE for PCV13 was estimated at 6.7% (95% CI, 5.9%-7.5%) for pneumonia, 4.7% (95% CI, 3.9%-5.6%) for non-HA pneumonia, and 5.8% (95% CI, 2.6%-8.9%) for LP. From September 2014 through December 2017, an estimated 35127 pneumonia (95% CI, 33011-37270), 24643 non-HA pneumonia (95% CI, 22761-26552), and 1294 LP (95% CI, 797-1819) hospitalizations were averted through PCV13 use. CONCLUSIONS AND RELEVANCE: The study results suggest that PCV13 use was associated with reduced pneumonia hospitalization among Medicare beneficiaries 65 years or older, many of whom had underlying medical conditions. Increased PCV13 coverage and use of recently approved higher-valent pneumococcal conjugate vaccines may avert additional pneumonia hospitalizations in adults.

INTRODUCTION: Antimicrobial stewardship (AMS) is an important strategy to control antimicrobial resistance. Resources are available to provide guidance for design and implementation of AMS programmes, however these may have limited applicability in resource-limited settings including those in Asia. This scoping review aims to identify context-specific domains and items for the development of a healthcare facility (HCF)-level tool to guide AMS implementation in Asia. METHODS AND ANALYSIS: This review is the first step in a larger project to assess AMS implementation, needs and gaps in Asia. We will employ a deductive qualitative approach to identify locally appropriate domains and items of AMS implementation guided by Nilsen and Bernhardsson's contextual dimensions. This process is also informed by discussions from a technical advisory group coordinated by the US Centers for Disease Control and Prevention to develop an AMS HCF-level assessment tool for low-income and middle-income countries. We will review English-language documents that discuss HCF-level implementation, including those describing frameworks, components/elements or recommendations for design, implementation or assessment globally and specific to Asia. We have performed the search in August-September 2021 including general electronic databases (MEDLINE, Embase, Web of Science and Google Scholar), region-specific databases, national action plans, grey literature sources and reference lists to identify eligible documents. Country-specific documents will be restricted to countries in three subregions: South Asia, East Asia and Southeast Asia. Codes and themes will be derived through a content analysis, classified following the predefined context dimensions and used for developing domains and items of the assessment tool. ETHICS AND DISSEMINATION: Results from this review will feed into our stepwise process for developing a context-specific HCF-level assessment tool for AMS programmes to assess the implementation status, identify intervention opportunities and monitor progress over time. The process will be done in consultation with local stakeholders, the end-users of the generated knowledge.

Implementation of antimicrobial stewardship programs (ASPs) in well-resourced countries has been associated with reductions in antibiotic-resistant infections and improved patient outcomes. Several guidance documents providing recommendations on how to structure antimicrobial stewardship activities at the national and hospital level in resource-limited settings have been published. However, few hospitals in Latin America report having a structure or resources needed for a successful ASP. Given the alarming increases in antimicrobial resistance in Latin America, better understanding of barriers to promote implementation of effective ASPs is urgently needed. We have summarized past and present antimicrobial stewardship activities in Latin American hospitals, and we describe key elements needed in future efforts to strengthen antimicrobial stewardship in the region. The Author(s), 2022.

BACKGROUND: As part of the global Invasive Bacterial Vaccine-Preventable Diseases Surveillance Network, 12 African countries referred cerebrospinal fluid (CSF) samples to South Africa's regional reference laboratory. We evaluated the utility of real-time polymerase chain reaction (PCR) in detecting and serotyping/grouping Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae (HNS). METHODS: From 2008 to 2017, CSF samples collected from children <5 years old with suspected meningitis underwent routine microbiology testing in-country, and 11 680 samples were submitted for HNS PCR at the regional reference laboratory. Unconditional logistic regression, with adjustment for geographic location, was performed to identify factors associated with PCR positivity. RESULTS: The overall HNS PCR positivity rate for all countries was 10% (1195 of 11 626 samples). In samples with both PCR and culture results, HNS PCR positivity was 11% (744 of 6747 samples), and HNS culture positivity was 3% (207 of 6747). Molecular serotype/serogroup was assigned in 75% of PCR-positive specimens (762 of 1016). Compared with PCR-negative CSF samples, PCR-positive samples were more often turbid (adjusted odds ratio, 6.80; 95% confidence interval, 5.67-8.17) and xanthochromic (1.72; 1.29-2.28), had elevated white blood cell counts (6.13; 4.71-7.99) and high protein concentrations (5.80; 4.34-7.75), and were more often HNS culture positive (32.70; 23.18-46.12). CONCLUSION: PCR increased detection of vaccine-preventable bacterial meningitis in countries where confirmation of suspected meningitis cases is impeded by limited culture capacity.

BACKGROUND: In 2013, the Dominican Republic introduced 13-valent pneumococcal conjugate vaccine (PCV13) using a 3-dose schedule (at 2, 4 and 12 months of age). We evaluated the impact of PCV13 on serotypes causing pneumococcal pneumonia with pleural effusion. METHODS: Surveillance data after PCV13 introduction (July 2014 to June 2016) were compared with data before PCV13 introduction (July 2009 to June 2011). Cases were defined as radiologic evidence of pneumonia with pleural effusion in a child aged <15 years. Pneumococcus was detected in pleural fluid by either culture or polymerase chain reaction, and serotyping was performed. The Ministry of Health's PCV13 uptake data for 2014-2016 were obtained. RESULTS: The prevalence of pneumococcus among cases was similar before and after PCV13 introduction (56.4% and 52.8%, respectively). The proportion of pneumococcal cases caused by vaccine serotypes was 86% for children <2 years old both before and PCV13 introduction. Compared with before PCV13, serotype 14 accounted for a smaller (28% vs 13%, respectively; P = .02) and serotype 1 for a larger (23% vs 37%; P = .09) proportion of pneumococcal cases after PCV13 introduction. National uptake for the first, second, and third PCV13 doses was 94%, 81%, and 28%, respectively, in 2014 and 75%, 61%, and 26% in 2015. DISCUSSION: While the decrease in pneumococcal pneumonia with pleural effusion caused by serotype 14 may reflect an early effect of PCV13 implementation, other vaccine serotypes, including serotype 1, are not well controlled. Better PCV13 coverage for all 3 doses is needed.