Antibiotic Stewardship Policies Research Articles

The pattern of antibiotic utilisation among intensive care unit patients hospitalised in a Gauteng (South African) provincial tertiary hospital: Comparing findings before and during COVID-19.

Various mechanisms may contribute to and direct the progression of antibiotic resistance. A prominent driver associated with antibiotic resistance is inappropriate use or consumption. The sudden emergence of coronavirus disease 2019 (COVID-19 ) changed the conventional practices related to antibiotic utilisation through repurposing the use of antibiotics. Apart from the implementation of antibiotic stewardship programmes, the pressure COVID-19 placed on healthcare systems resulted in poor prescribing and medication review practices, potentially exacerbating antibiotic resistance. Furthermore, the public health system has issues that make it difficult to routinely monitor, quantify antibiotic consumption, and offer evaluation, feedback and intervention, particularly in low- and middle- income countries such as South Africa (SA). Therefore, this study aimed to determine antibiotic utilisation before and during the COVID-19 pandemic in a Gauteng provincial tertiary hospital (GPTH) in SA. To determine, examine, and compare antibiotic consumption among intensive care unit (ICU) patients admitted to a GPTH during the pre-COVID-19 period and during the COVID-19 pandemic, in addition to determining the prevalence of the World Health Organisation (WHO) 'watch' category antibiotics before and following the emergence of COVID-19 . A retrospective cross-sectional data analysis was undertaken of 335 medical files of ICU patients hospitalised in a GPTH between January 2017 and December 2021. Descriptive statistics were used to examine patient characteristics and antibiotic prescribing variables (antibiotic selection, dosage, route of administration, frequency, duration of course and indication for which antibiotic was prescribed). The study found that the most frequently prescribed antibiotics were amoxicillin in combination with clavulanate (pre-pandemic 31.99%; amid-COVID-19 38.43%), followed by ceftriaxone (pre-pandemic 15.44%; amid-COVID-19 14.55%), piperacillin in combination with tazobactam (pre-pandemic 11.40%; amid-COVID-19 8.58%) and azithromycin (pre-pandemic 7.725%; amid-COVID-19 19.78%). The macrolide and penicillin (in combination with a beta-lactamase inhibitor) classes demonstrated an increase in consumption from the pre-pandemic period moving into the COVID-19 pandemic. This highlights the need for improved antibiotic stewardship programmes and policies to combat inappropriate and unnecessary antibiotic usage.

Antibiotic usage patterns in COVID-19 patients in five tertiary hospitals from Bangladesh: A countrywide picture

ObjectivesIrrational and injudicious use of antibiotics in COVID-19 patients could be detrimental in a tropical country with a weak antibiotic stewardship policy such as Bangladesh. This study aimed to focus on the antibiotic usage patterns in COVID-19 patients in Bangladesh. MethodsThis prospective observational study was performed from July 2020 to June 2021 in five tertiary hospitals in Bangladesh. Data on demographic profile, disease severity, and antibiotic usage were collected directly from the patients’ hospital documents. ResultsA total of 3486 (94.4%) patients were treated with at least one antibiotic; 3261 (93.6%) patients received a single antibiotic, and 225 (6.5%) received multiple antibiotics. The most used antibiotics were ceftriaxone (37.3%), co-amoxiclav (26.3%), azithromycin (10.6%), and meropenem (10.3%). According to the World Health Organization AWaRe categorization, most (2260; 69.6%) of the antibiotics prescribed in this study belonged to the “Watch” group. Culture and sensitivity reports were available in 111 cases from one center. Only 18.9% of the patients were found to be co-infected with multi-drug-resistant bacteria (52.4% yield from sputum, 28.6% from urine, and 14.3% from blood). ConclusionsStrict antibiotic prescribing policy and antibiotic stewardship should be implemented immediately to limit the future threat of antimicrobial resistance in countries such as Bangladesh.

Significantly reduced duration of antibiotic prescription for erysipelas subsequent to the 2019 French guidelines on skin and soft tissue infection: A before-after study

BackgroundNew skin and soft tissue infections (SSTI) guidelines were published in 2019 in France, changing the recommended duration for antibiotic treatment. The objective of the present study was to assess the impact of the publication of the 2019 French guidelines on SSTIs on the duration of antibiotic prescription for erysipelas. MethodsIn a before-after study (a year before and a year after April 1st, 2019), we included all adult patients diagnosed with erysipelas in Reims University Hospital medical wards and the emergency department. We retrospectively retrieved antibiotic prescription duration in the patients’ medical files. ResultsAmong 50 patients in the “before” and 39 in the “after” group, the mean duration of antibiotic prescription was significantly shorter in the “after” group (9.4 ± 2.8 vs. 12.4 ± 3.8 days, p = 0.0001). ConclusionsA 25% decrease in the duration of antibiotic prescription for erysipelas was observed following the implementation of these guidelines, providing useful information for an antibiotic stewardship policy.

Antimicrobial stewardship capacity and antibiotic utilisation practices in the Cape Coast Teaching Hospital, Ghana: A point prevalence survey study.

Antimicrobial resistance (AMR) is a global threat that necessitates coordinated strategies to improve antibiotic prescribing and reduce AMR. A key activity is ascertaining current prescribing patterns in hospitals to identify targets for quality improvement programmes. The World Health Organisation point prevalence survey methodology was used to assess antibiotic prescribing in the Cape Coast Teaching Hospital. All core variables identified by the methodology were recorded. A total of 78.8% (82/104) patients were prescribed at least one antibiotic, with the majority from adult surgical wards (52.14%). Significantly longer hospital stays were associated with patients who underwent surgery (p = 0.0423). "Access" antibiotics dominated total prescriptions (63.8%, 132/207) with ceftriaxone, cefuroxime, and ciprofloxacin being the most prescribed "Watch" antibiotics. The most common indications were for medical prophylaxis (59.8%, 49/82) and surgical prophylaxis (46.3%, 38/82). Over one-third of surgical prophylaxis (34.2%, 13/38) indications extended beyond one day. There was moderate documentation of reasons for antibiotic treatment in patient notes (65.9%, 54/82), and targeted therapy after samples were taken for antimicrobial susceptibility testing (41.7%, 10/24). Guideline compliance was low (25%) where available. There was high use of antibiotics within the hospital which needs addressing. Identified quality targets include developing surgical prophylaxis guidelines, reviewing "Watch" antibiotic prescribing, and assessing antibiotic durations for patients on two or more antibiotics. Organizational-level deficiencies were also identified that need addressing to help instigate ASPs. These can be addressed by developing local prescribing protocols and antibiotic stewardship policies in this hospital and wider in Ghana and across Africa.

A Comparative Evaluation of ESBL Production and Carbapenem Resistance in UTIs Before and During COVID-19

Background: The COVID-19 pandemic has heightened the urgency to address antibiotic resistance, particularly ESBL and carbapenem-resistant UTIs. Our study seeks to assess the pandemic's effect on the prevalence of these resistances, comparing data from before and during COVID-19. By identifying trends in resistance patterns, we aim to enhance antibiotic stewardship and inform healthcare policies. Understanding the pandemic's impact on ESBL and carbapenem resistance is vital for guiding clinical practices and public health initiatives in tackling antibiotic resistance. Methods: This retrospective study, conducted at King Fahad Medical City in Riyadh, Saudi Arabia, analyzed positive urine cultures from January 2018 to December 2022 to assess the prevalence of antibiotic resistance among UTIs. Using WHO-recommended semiquantitative culturing methods on CLED and blood agar, bacterial isolates were identified via the BD Phoenix system and antimicrobial susceptibility was assessed following CLSI guidelines. ESBL detection employed the Double-Disc Synergy Test. Data analysis involved SPSS for statistical evaluation, utilizing chi-square and t-tests for categorical and continuous variables, respectively, and logistic regression to explore associations between variables and antibiotic resistance, with significance set at p

Phenotypic antibiotic susceptibility profile of clinical Enterobacteriaceae isolates from Kaduna State, northwest Nigeria.

Background. The increasing resistance of clinical Enterobacteriaceae isolates to commonly prescribed antibiotics has been reported around the world. Data are generally lacking on the prevalence and antibiotic susceptibility profile of clinical Enterobacteriaceae isolates from Kaduna, northwest Nigeria. This study thus aimed to determine the diversity and antibiotic resistance profile of clinical Enterobacteriaceae isolates recovered from clinical specimens from patients admitted to two selected healthcare institutions in Kaduna. Methods. This was a prospective cross-sectional study conducted between September and December 2021. Non-duplicate clinical bacterial isolates recovered from various specimens were collected and identified using rapid biochemical identification kits. The susceptibility of identified Enterobacteriaceae to various antibiotics and phenotypic detection of carbapenemase enzymes were thereafter determined. The data were analysed and visualized using R software version 4.3.1. Results. Of the 500 bacterial isolates recovered from specimens collected for the purpose of clinical bacteriology diagnostics, 108 (21.6 %) were identified as Enterobacteriaceae, with Pantoea agglomerans (52, 48.1 %) and Klebsiella oxytoca (19, 17.6 %) being the most prevalent. The isolates exhibited high resistance to azithromycin (69 %) and ceftazidime (42 %), while exhibiting low resistance to amikacin (7 %) and imipenem (10 %). Among the carbapenem-resistant Enterobacteriaceae (CRE) isolates, a significant proportion (12/17, 70.6 %) tested positive for carbapenemase activity. Conclusion. This study reports a high prevalence of multidrug-resistant Enterobacteriaceae in Kaduna, northwest Nigeria. The emergence of pathogenic P. agglomerans and an alarmingly high prevalence of carbapenemase-producing CRE were also observed. The presence of carbapenemase producers in an area with low carbapenem usage and resistance rates raises significant concerns. Continuous surveillance and robust antibiotic stewardship policies are imperative to preserve the efficacy of carbapenems in this region.

Antimicrobial resistance rates of urogenital Mycoplasma hominis and Ureaplasma species before and during the COVID-19 pandemic: results from a Greek survey, 2014 to 2022.

The prevalence of antibiotic-resistant urogenital mycoplasmas and ureaplasmas has been gradually increasing over the years, leading to greater concern for accurate diagnosis and treatment. In this study, the antimicrobial resistance trends in Greece were analyzed using 2992 Ureaplasma spp. and 371 M. hominis isolates collected between 2014 and 2022. Antibiotic sensitivity was determined using eight different antimicrobial agents (josamycin, pristinamycin, clindamycin, ofloxacin, azithromycin, tetracycline, erythromycin, and doxycycline), with the data analyzed using descriptive statistical methods. Resistance rates to clindamycin and erythromycin increased for both M. hominis and Ureaplasma spp., while remaining relatively low for Tetracycline, Doxycycline, and Ofloxacin. For Ureaplasma spp., high susceptibility was observed to pristinamycin, tetracycline, doxycycline, azithromycin, and josamycin, and intermediate susceptibility to erythromycin. However, the resistance rate for clindamycin dramatically increased from 60% in 2014 to a peak of 98.46% in 2021, and the erythromycin resistance rate increased from 9.54% in 2018 to 22.13% in 2021. M. hominis exhibited consistently high resistance rates to Erythromycin, while Azithromycin resistance significantly increased over time, from 52.78% in 2017 to 97.22% in 2022. The alarming escalation in antibiotic-resistant urogenital mycoplasmas and ureaplasmas in the Greek population is a significant concern. Antibiotic overconsumption may have played a crucial role in increasing resistance trends. The implementation of nationwide surveillance systems, proper antibiotic stewardship policies, and appropriate culture-based therapy policies are necessary to effectively control this emerging risk.

The impact of the COVID-19 pandemic on the treatment of common infections in primary care and the change to antibiotic prescribing in England

BackgroundThere is concern that the COVID-19 pandemic altered the management of common infections in primary care. This study aimed to evaluate infection-coded consultation rates and antibiotic use during the pandemic and how any change may have affected clinical outcomes.MethodsWith the approval of NHS England, a retrospective cohort study using the OpenSAFELY platform analysed routinely collected electronic health data from GP practices in England between January 2019 and December 2021. Infection coded consultations and antibiotic prescriptions were used estimate multiple measures over calendar months, including age-sex adjusted prescribing rates, prescribing by infection and antibiotic type, infection consultation rates, coding quality and rate of same-day antibiotic prescribing for COVID-19 infections. Interrupted time series (ITS) estimated the effect of COVID-19 pandemic on infection-coded consultation rates. The impact of the pandemic on non- COVID-19 infection-related hospitalisations was also estimated.ResultsRecords from 24 million patients were included. The rate of infection-related consultations fell for all infections (mean reduction of 39% in 2020 compared to 2019 mean rate), except for UTI which remained stable. Modelling infection-related consultation rates highlighted this with an incidence rate ratio of 0.44 (95% CI 0.36–0.53) for incident consultations and 0.43 (95% CI 0.33–0.54) for prevalent consultations. Lower respiratory tract infections (LRTI) saw the largest reduction of 0.11 (95% CI 0.07–0.17). Antibiotic prescribing rates fell with a mean reduction of 118.4 items per 1000 patients in 2020, returning to pre-pandemic rates by summer 2021. Prescribing for LRTI decreased 20% and URTI increased 15.9%. Over 60% of antibiotics were issued without an associated same-day infection code, which increased during the pandemic. Infection-related hospitalisations reduced (by 62%), with the largest reduction observed for pneumonia infections (72.9%). Same-day antibiotic prescribing for COVID-19 infection increased from 1 to 10.5% between the second and third national lockdowns and rose again during 2022.ConclusionsChanges to consultations and hospital admissions may be driven by reduced transmission of non-COVID-19 infections due to reduced social mixing and lockdowns. Inconsistencies in coding practice emphasises the need for improvement to inform new antibiotic stewardship policies and prevent resistance to novel infections.

Complications of local anaesthetic transperineal ultrasound‐guided prostate biopsy: A systematic literature review

AbstractThe prostate cancer pathway has evolved rapidly over the last decade responding to evidence‐based recommendations. These changes were accelerated further over the last 5 years due to the Covid‐19 pandemic and the antibiotic stewardship policies regarding nosocomial/iatrogenic infections. Local anaesthetic transperineal ultrasound‐guided biopsy is a relatively new technique that became gold‐standard practice for prostate cancer diagnosis due to decreased sepsis rates. However, data that justified its implementation was more focused on its efficacy and clinically significant cancer detection rates, lacking robust methodological complications data, including in some cases the utilization of validated tools to assess complications. In patients subjected to local anaesthetic transperineal ultrasound‐guided prostate biopsies, what are the most recent reported complications? This systematic literature review followed Bettany‐Saltikov and McSherry's Manual guidance for systematic literature reviews. Patient/target, Intervention, Comparison, Outcome (PICO) research method, and Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) were used to structure the search strategy and report results. This review was conducted using PubMed/Medline, Excerpa Medica database (EMBASE), and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases. Inclusion criteria focused on recent studies which matched current national and international prostate cancer pathway guidelines (National Institute for Health and Care Excellence and European Association of Urology). Quality assessments were performed using Critical Appraisal Skills Programme checklists. Four cohort studies were included in this review. A total of 946 men were submitted to local anaesthetic transperineal prostate biopsy. Patient experience showed procedure was tolerated with the most painful part of the procedure being local anaesthetic infiltration with Visual Analogue Score variation [2–5]. Few complications were reported. Haematuria had broad definitions across studies, being difficult to interpret the results of this complication. Only one case reported gross haematuria leading to acute urinary retention. Historically, acute urinary retention was mentioned as one of the main adverse effects of transperineal biopsies. However, in this systematic literature review it had similar incidence as transrectal biopsies, particularly when local anaesthesia was utilized. Lower urinary tract symptoms and erectile dysfunction seemed to not be affected by prostate biopsy procedures, however, more data is required as only two studies addressed these issues. Six urinary tract infection patients were reported (0.63%), and one urosepsis case (0.10%). This seems to demonstrate few urinary infections occur and fewer sepsis cases, particularly when compared with transrectal biopsies data, concurring with previous research. Marginal difference was noted between infection rates with or without antibiotic prophylaxis. Local anaesthetic transperineal ultrasound‐guided prostate biopsies seem to remain a safe procedure from a complications rate point of view. It has been proven before to have fewer urinary tract infections and sepsis episodes. Low‐risk patients can have LATPUS biopsies without antibiotic prophylaxis. High‐risk patients need clinician assessment and judicious utilization of antibiotics. Other complications require further studies with standardized biopsy techniques, clear complication definitions, and use of validated tools to measure complications.

ACORN (A Clinically-Oriented Antimicrobial Resistance Surveillance Network) II: protocol for case based antimicrobial resistance surveillance.

Background: Antimicrobial resistance surveillance is essential for empiric antibiotic prescribing, infection prevention and control policies and to drive novel antibiotic discovery. However, most existing surveillance systems are isolate-based without supporting patient-based clinical data, and not widely implemented especially in low- and middle-income countries (LMICs). Methods: A Clinically-Oriented Antimicrobial Resistance Surveillance Network (ACORN) II is a large-scale multicentre protocol which builds on the WHO Global Antimicrobial Resistance and Use Surveillance System to estimate syndromic and pathogen outcomes along with associated health economic costs. ACORN-healthcare associated infection (ACORN-HAI) is an extension study which focuses on healthcare-associated bloodstream infections and ventilator-associated pneumonia. Our main aim is to implement an efficient clinically-oriented antimicrobial resistance surveillance system, which can be incorporated as part of routine workflow in hospitals in LMICs. These surveillance systems include hospitalised patients of any age with clinically compatible acute community-acquired or healthcare-associated bacterial infection syndromes, and who were prescribed parenteral antibiotics. Diagnostic stewardship activities will be implemented to optimise microbiology culture specimen collection practices. Basic patient characteristics, clinician diagnosis, empiric treatment, infection severity and risk factors for HAI are recorded on enrolment and during 28-day follow-up. An R Shiny application can be used offline and online for merging clinical and microbiology data, and generating collated reports to inform local antibiotic stewardship and infection control policies. Discussion: ACORN II is a comprehensive antimicrobial resistance surveillance activity which advocates pragmatic implementation and prioritises improving local diagnostic and antibiotic prescribing practices through patient-centred data collection. These data can be rapidly communicated to local physicians and infection prevention and control teams. Relative ease of data collection promotes sustainability and maximises participation and scalability. With ACORN-HAI as an example, ACORN II has the capacity to accommodate extensions to investigate further specific questions of interest.

Genomic insight into the distribution and genetic environment of blaIMP-4 in clinical carbapenem-resistant Klebsiella pneumoniae strains in China

Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a major threat to public health due to its resistance to almost all antibiotics. It is associated with substantial morbidity and mortality and poses a significant challenge to healthcare systems around the globe. Based on our previous nationwide survey of carbapenem-resistant Enterobacteriaceae (CRE) in China, seven blaIMP-4-carrying CRKP isolates were identified, all exhibiting MDR and epidemiologically linked to four different regions in China. WGS analysis revealed that the seven blaIMP-4 genes were all located on plasmids, of which five blaIMP-4 genes were located on the IncHI5 plasmids and the other two belonged to the IncN and IncFIIK plasmids, respectively. Except for the IncHI5 plasmid, conjugation assays revealed that the IncN and IncFIIK plasmids could be transferred to the recipient strain Escherichia coli J53. This study revealed significant genetic variation and identified numerous resistance factors among blaIMP-4-carrying CRKP strains in China, suggesting that blaIMP-4-carrying CRKP strains evolved via multiple phylogenetic routes and highlighting a need for expanded surveillance and establishment of control measures to prevent dissemination of CRKP strains, and facilitate development of more effective antibiotic stewardship policies and infection control programs.

Effect of a national antibiotic stewardship intervention in China targeting carbapenem overuse: An interrupted time-series analysis

To assess trends and patterns of carbapenem use and to evaluate the effects of a nationwide antibiotic stewardship policy to reduce carbapenem overuse. In this quasi-experimental study, using longitudinal data from the national drug procurement database and interrupted time-series analyses with carbapenems as the intervention group and possible carbapenem substitutes as the comparison group, we evaluated the effects of a national stewardship policy on carbapenem consumption and expenditures, by region and types of healthcare institutions. The carbapenem procurement volume declined by -28.8% (95% CI -35.0 to -22.6) (-334.4 thousand defined daily doses [DDDs] per month), and carbapenem expenditures showed a relative reduction of -38.1% (-43.9 to -32.2). The gap between the use of carbapenems and each drug in the comparison group narrowed after the policy intervention, with an increase in tigecycline use (14.9 thousand DDDs [10.8-18.9]) and a slower decrease in use of certain third-generation cephalosporin combinations (-85.7 [-143.0 to -28.4]), penicillin combinations (-200.9 [-421.4-19.6]), and fourth-generation cephalosporins (-116.9 [-219.8 to -14.0]). Consumption was highest during the pre-policy period, and declines were largest following the intervention in the eastern region (-32.1%, -39.8 to -24.4) and among tertiary hospitals (-266.2 [-339.5 to -192.9] thousand DDDs per month). This population-level drug utilization research represents the first comprehensive evaluation of the effectiveness of China's nationwide carbapenem stewardship. The national policy targeting carbapenem prescribing has led to a sustained reduction in carbapenem use with limited substitution. Effects varied geographically and were concentrated in tertiary and secondary hospitals.

Implications of reducing antibiotic treatment duration for antimicrobial resistance in hospital settings: A modelling study and meta-analysis.

Reducing antibiotic treatment duration is a key component of hospital antibiotic stewardship interventions. However, its effectiveness in reducing antimicrobial resistance is uncertain and a clear theoretical rationale for the approach is lacking. In this study, we sought to gain a mechanistic understanding of the relation between antibiotic treatment duration and the prevalence of colonisation with antibiotic-resistant bacteria in hospitalised patients. We constructed 3 stochastic mechanistic models that considered both between- and within-host dynamics of susceptible and resistant gram-negative bacteria, to identify circumstances under which shortening antibiotic duration would lead to reduced resistance carriage. In addition, we performed a meta-analysis of antibiotic treatment duration trials, which monitored resistant gram-negative bacteria carriage as an outcome. We searched MEDLINE and EMBASE for randomised controlled trials published from 1 January 2000 to 4 October 2022, which allocated participants to varying durations of systemic antibiotic treatments. Quality assessment was performed using the Cochrane risk-of-bias tool for randomised trials. The meta-analysis was performed using logistic regression. Duration of antibiotic treatment and time from administration of antibiotics to surveillance culture were included as independent variables. Both the mathematical modelling and meta-analysis suggested modest reductions in resistance carriage could be achieved by reducing antibiotic treatment duration. The models showed that shortening duration is most effective at reducing resistance carriage in high compared to low transmission settings. For treated individuals, shortening duration is most effective when resistant bacteria grow rapidly under antibiotic selection pressure and decline rapidly when stopping treatment. Importantly, under circumstances whereby administered antibiotics can suppress colonising bacteria, shortening antibiotic treatment may increase the carriage of a particular resistance phenotype. We identified 206 randomised trials, which investigated antibiotic duration. Of these, 5 reported resistant gram-negative bacteria carriage as an outcome and were included in the meta-analysis. The meta-analysis determined that a single additional antibiotic treatment day is associated with a 7% absolute increase in risk of resistance carriage (80% credible interval 3% to 11%). Interpretation of these estimates is limited by the low number of antibiotic duration trials that monitored carriage of resistant gram-negative bacteria, as an outcome, contributing to a large credible interval. In this study, we found both theoretical and empirical evidence that reducing antibiotic treatment duration can reduce resistance carriage, though the mechanistic models also highlighted circumstances under which reducing treatment duration can, perversely, increase resistance. Future antibiotic duration trials should monitor antibiotic-resistant bacteria colonisation as an outcome to better inform antibiotic stewardship policies.

The vanRCd Mutation 343A>G, Resulting in a Thr115Ala Substitution, Is Associated with an Elevated Minimum Inhibitory Concentration (MIC) of Vancomycin in Clostridioides difficile Clinical Isolates from Florida.

Clostridioides difficile, the primary cause of nosocomial antibiotic-associated diarrhea, has a complex relationship with antibiotics. While the use of broad-spectrum antibiotics disrupts the gut microbiota and increases the risk of C. difficile infection (CDI), antibiotics are also the primary treatment for CDI. However, only a few antibiotics, including vancomycin, fidaxomicin, and rifaximin, are effective against CDI, and resistance to these antibiotics has emerged recently. In this study, we report the identification of two RT027 C. difficile clinical isolates (TGH35 and TGH64) obtained from symptomatic CDI-diagnosed patients in Tampa, Florida in 2016. These two strains showed an elevated minimum inhibitory concentration (MIC) of vancomycin (MIC = 4 μg/mL, compared to the EUCAST breakpoint of 2 μg/mL) and contained a vanRCd 343A>G mutation resulting in a Thr115Ala substitution in the VanRCd response regulator. This mutation was absent in the vancomycin-sensitive control epidemic strain RT027/R20291. TGH64 was also resistant to rifaximin (MIC ≥ 128 μg/mL) and carried the previously reported Arg505Lys and Ile548Met mutations in RpoB. Furthermore, we report on the antimicrobial resistance (AMR) and genomic characterization of additional C. difficile isolates, including RT106/TGH120, RT017/TGH33, and RT017/TGH51, obtained from the same patient sample cohort representing the highly prevalent and regionally distributed C. difficile ribotypes worldwide. Considering that the VanRCd Thr115Ala mutation was also independently reported in seven C. difficile clinical isolates from Texas and Israel in 2019, we recommend epidemiological surveillance to better understand the impact of this mutation on vancomycin resistance. IMPORTANCE The perpetually evolving antimicrobial resistance (AMR) of C. difficile is an important contributor to its epidemiology and is a grave concern to global public health. This exacerbates the challenge of treating the infections caused by this multidrug-resistant causative organism of potentially life-threatening diarrhea. Further, the novel resistance-determining factors can be transferred between different strains and species of bacteria and cause the spread of AMR in clinical, environmental, and community settings. In this study, we have identified a mutation (vanRCd 343A>G) that causes a Thr115Ala substitution and is linked to an increased MIC of vancomycin in clinical isolates of C. difficile obtained from Florida in 2016. Understanding the mechanisms of AMR, especially those of newly evolving strains, is essential to effectively guide antibiotic stewardship policies to combat antibiotic resistance as well as to discover novel therapeutic targets.

ACORN (A Clinically-Oriented Antimicrobial Resistance Surveillance Network) II: protocol for case based antimicrobial resistance surveillance

Background: Antimicrobial resistance surveillance is essential for empiric antibiotic prescribing, infection prevention and control policies and to drive novel antibiotic discovery. However, most existing surveillance systems are isolate-based without supporting patient-based clinical data, and not widely implemented especially in low- and middle-income countries (LMICs). Methods: A Clinically-Oriented Antimicrobial Resistance Surveillance Network (ACORN) II is a large-scale multicentre protocol which builds on the WHO Global Antimicrobial Resistance and Use Surveillance System to estimate syndromic and pathogen outcomes along with associated health economic costs. ACORN-healthcare associated infection (ACORN-HAI) is an extension study which focuses on healthcare-associated bloodstream infections and ventilator-associated pneumonia. Our main aim is to implement an efficient clinically-oriented antimicrobial resistance surveillance system, which can be incorporated as part of routine workflow in hospitals in LMICs. These surveillance systems include hospitalised patients of any age with clinically compatible acute community-acquired or healthcare-associated bacterial infection syndromes, and who were prescribed parenteral antibiotics. Diagnostic stewardship activities will be implemented to optimise microbiology culture specimen collection practices. Basic patient characteristics, clinician diagnosis, empiric treatment, infection severity and risk factors for HAI are recorded on enrolment and during 28-day follow-up. An R Shiny application can be used offline and online for merging clinical and microbiology data, and generating collated reports to inform local antibiotic stewardship and infection control policies. Discussion: ACORN II is a comprehensive antimicrobial resistance surveillance activity which advocates pragmatic implementation and prioritises improving local diagnostic and antibiotic prescribing practices through patient-centred data collection. These data can be rapidly communicated to local physicians and infection prevention and control teams. Relative ease of data collection promotes sustainability and maximises participation and scalability. With ACORN-HAI as an example, ACORN II has the capacity to accommodate extensions to investigate further specific questions of interest.

Regional and national antimicrobial stewardship activities: a survey from the Joint Programming Initiative on Antimicrobial Resistance-Primary Care Antibiotic Audit and Feedback Network (JPIAMR-PAAN).

Antibiotic overuse and misuse in primary care are common, highlighting the importance of antimicrobial stewardship (AMS) efforts in this setting. Audit and feedback (A&F) interventions can improve professional practice and performance in some settings. To leverage the expertise from international members of the Joint Programming Initiative on Antimicrobial Resistance - Primary care Antibiotic Audit and feedback Network (JPIAMR-PAAN). Network members all have experience of designing and delivering A&F interventions to reduce inappropriate antibiotic prescribing in primary care settings. We aim to introduce the network and explore ongoing A&F activities in member regions. An online survey was administered to all network members to collect regional information. Fifteen respondents from 11 countries provided information on A&F activities in their country, and national/regional antibiotic stewardship programmes or policies. Most countries use electronic medical records as the primary data source, antibiotic appropriateness as the main outcome of feedback, and target GPs as the prescribers of interest. Funding sources varied across countries, which could influence the frequency and quality of A&F interventions. Nine out of 11 countries reported having a national antibiotic stewardship programme or policy, which aim to provide systematic support to ongoing AMS efforts and aid sustainability. The survey identified gaps and opportunities for AMS efforts that include A&F across member countries in Europe, Canada and Australia. JPIAMR-PAAN will continue to leverage its members to produce best practice resources and toolkits for antibiotic A&F interventions in primary care settings and identify research priorities.

Relationship between antibiotic consumption pattern and antibiotic resistance in neonatal sepsis.

Inappropriate use of antibiotics may increase antimicrobial resistance (AMR) among different microorganisms and may lead to treatment failure in neonatal septicemia. The aim of this study was to recognize the most common microorganisms responsible for neonatal sepsis and to evaluate the trend of change of resistance pattern among microorganisms. This study was done retrospectively on 344 cases diagnosed with neonatal sepsis, including both early and late onset cases, admitted to the tertiary care teaching hospital of southern India from January 2012 to July 2017. Accordingly, 231 culture positive neonatal sepsis cases were collected from hospital data base and analyzed. Culture positive cases within 72 hours of life were termed as early onset while after 72 hours were late onset. Antibiotics utilization during the period was calculated using WHO AMC tool and reported as (DDD)/100 bed days. Klebsiella pneumoniae with 56 (21.8%) and Coagulase negative Staphylococcus with 52 (20.2%) cases were the most frequent isolated organisms which were responsible for 55.8% and 14.6% of deaths among the study subjects respectively. Amikacin (86.7%), vancomycin (52.3%) and ampicillin (40.6%) were the most used antibiotics in terms of DDD/100 bed days. The results obtained from our study have brought substantial information on the antibiotic resistance pattern among microorganisms causing neonatal sepsis. Moreover, results obtained from this study can be used for designing antibiotic stewardship policies to prevent the emergence of resistance and to improve the treatment outcome.

Bacterial co-infection and antibiotic stewardship in patients with COVID-19: a systematic review and meta-analysis

IntroductionUnderstanding the proportion of patients with COVID-19 who have respiratory bacterial co-infections and the responsible pathogens is important for managing COVID-19 effectively while ensuring responsible antibiotic use.ObjectiveTo estimate the frequency of bacterial co-infection in COVID-19 hospitalized patients and of antibiotic prescribing during the early pandemic period and to appraise the use of antibiotic stewardship criteria.MethodsSystematic review and meta-analysis was performed using major databases up to May 5, 2021. We included studies that reported proportion/prevalence of bacterial co-infection in hospitalized COVID-19 patients and use of antibiotics. Where available, data on duration and type of antibiotics, adverse events, and any information about antibiotic stewardship policies were also collected.ResultsWe retrieved 6,798 studies and included 85 studies with data from more than 30,000 patients. The overall prevalence of bacterial co-infection was 11% (95% CI 8% to 16%; 70 studies). When only confirmed bacterial co-infections were included the prevalence was 4% (95% CI 3% to 6%; 20 studies). Overall antibiotic use was 60% (95% CI 52% to 68%; 52 studies). Empirical antibiotic use rate was 62% (95% CI 55% to 69%; 11 studies). Few studies described criteria for stopping antibiotics.ConclusionThere is currently insufficient evidence to support widespread empirical use of antibiotics in most hospitalised patients with COVID-19, as the overall proportion of bacterial co-infection is low. Furthermore, as the use of antibiotics during the study period appears to have been largely empirical, clinical guidelines to promote and support more targeted administration of antibiotics in patients admitted to hospital with COVID-19 are required.

Bacterial Pathogens in the Food Industry: Antibiotic Resistance and Virulence Factors of Salmonella enterica Strains Isolated from Food Chain Links.

Salmonella is one of the most important foodborne pathogens. Fifty-three strains of Salmonella deposited in the Culture Collection of Industrial Microorganisms-Microbiological Resources Center (IAFB) were identified using molecular and proteomic analyses. Moreover, the genetic similarity of the tested strains was determined using the PFGE method. Main virulence genes were identified, and phenotypical antibiotic susceptibility profiles and prevalence of resistance genes were analyzed. Subsequently, the occurrence of the main mechanisms of β-lactam resistance was determined. Virulence genes, invA, fimA, and stn were identified in all tested strains. Phenotypic tests, including 28 antibiotics, showed that 50.9% of the strains were MDR. The tet genes associated with tetracyclines resistance were the most frequently identified genes. Concerning the genes associated with ESBL-producing Salmonella, no resistance to the TEM and CTX-M type was identified, and only two strains (KKP 1597 and KKP 1610) showed resistance to SHV. No strains exhibited AmpC-type resistance but for six Salmonella strains, the efflux-related resistance of PSE-1 was presented. The high number of resistant strains in combination with multiple ARGs in Salmonella indicates the possible overuse of antibiotics. Our results showed that it is necessary to monitor antimicrobial resistance profiles in all food chain links constantly and to implement a policy of proper antibiotic stewardship to contain or at least significantly limit the further acquisition of antibiotic resistance among Salmonella strains.

Molecular Characterization and Antibiogram of Acinetobacter baumannii Clinical Isolates Recovered from the Patients with Ventilator-Associated Pneumonia.

A 2-year prospective study carried out on ventilator-associated pneumonia (VAP) patients in the intensive care unit at a tertiary care hospital, Hail, Kingdom of Saudi Arabia (KSA), revealed a high prevalence of extremely drug-resistant (XDR) Acinetobacter baumannii. About a 9% increase in the incidence rate of A. baumannii occurred in the VAP patients between 2019 and 2020 (21.4% to 30.7%). In 2019, the isolates were positive for IMP-1 and VIM-2 (31.1% and 25.7%, respectively) as detected by PCR. In comparison, a higher proportion of isolates produced NDM-1 in 2020. Here, we observed a high proportion of resistant ICU isolates towards the most common antibiotics in use. Colistin sensitivity dropped to 91.4% in the year 2020 as compared to 2019 (100%). Thus, the finding of this study has a highly significant clinical implementation in the clinical management strategies for VAP patients. Furthermore, strict implementation of antibiotic stewardship policies, regular surveillance programs for antimicrobial resistance monitoring, and screening for genes encoding drug resistance phenotypes have become imperative.