Antimicrobial stewardship programs in seven Latin American countries: facing the challenges.

BACKGROUND: Studies have shown that more than 50% of the antibiotics used in hospitals are unnecessary or inappropriate and, that antimicrobial resistance may cost up to 20 billion USD in excess medical costs each year. On the other hand, Antimicrobial Stewardship Programs (ASP) significantly reduce inappropriate antimicrobial use, emergence of antimicrobial resistance, healthcare associated infections, and costs in hospital settings. OBJECTIVE: To evaluate the development of ASP and antibiotic savings in 7 Latin American hospitals using standardized quantitative indicators in all the participating health care institutions. METHODS: An interventional study was conducted, where pre- and post- evaluations were performed using a standardized score tool adapted from the Joint Commission International accreditation standards and, the Colombian Institute of Technical Standards and Certification. We evaluated ASP from 7 Latin American hospitals between 2019 and 2020. A pre-intervention evaluation was done in each hospital to quantify the degree of development of the ASP (ASP Development score). Based on these results, tailored on-site training was implemented in each hospital, followed by a post-intervention evaluation to quantify improvement of ASP-development indicators. In addition, monetary savings in antimicrobials derived from the ASP intervention were estimated. RESULTS: In the pre-intervention evaluation, the average ASP development score for the 7 institutions was 65.8% (40-94.3%). The items with the lowest development score were those related to monitoring and communicating the ASP progress and success. For the post-intervention evaluation, 2 institutions couldn't participate due to the pressure imposed by the COVID-19 pandemic. For the remaining 5/7 hospitals, the average ASP development score was 82.3% with an increase of 12.0% when compared to the pre-intervention measurement of the same institutions (average pre-intervention score 70.3% (48.2%-94.3%) The items with a significant increase were key performance indicators, AMS education and training of the prescribers. Three of the seven (3/7) hospitals reported antibiotic monetary savings associated to the ASP intervention. CONCLUSIONS: The use of the tool described shown to be useful to evaluate specific areas of ASP-development that were lacking and tailor interventions for the participating hospitals, consequently, it helped improve ASP-development in the institutions that underwent pre- intervention and post-intervention analysis. In addition, the strategies showed monetary savings on antimicrobial costs when measured.

Use of Antibiotics Within the Last 14 Days of Life in Korean Patients: A Nationwide Study.

BACKGROUND: Antimicrobial prescriptions for serious chronic or acute illness nearing its end stages raise concerns about the potential for futile use, adverse events, increased multidrug-resistant organisms, and significant patient and social cost burdens. This study investigated the nationwide situation of how antibiotics are prescribed to patients during the last 14 days of life to guide future actions. METHODS: This nationwide multicenter retrospective cohort study was conducted at 13 hospitals in South Korea from November 1 to December 31, 2018. All decedents were included in the study. Antibiotic use during the last two weeks of their lives was investigated. RESULTS: A total of 1,201 (88.9%) patients received a median of two antimicrobial agents during the last two weeks of their lives. Carbapenems were prescribed to approximately half of the patients (44.4%) in the highest amount (301.2 days of therapy per 1,000 patient-days). Among the patients receiving antimicrobial agents, 63.6% were inappropriate and only 327 patients (27.2%) were referred by infectious disease specialists. The use of carbapenem (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.13-2.03; P = 0.006), underlying cancer (OR, 1.56; 95% CI, 1.20-2.01, P = 0.047), underlying cerebrovascular disease (OR, 1.88; 95% CI, 1.23-2.89, P = 0.004), and no microbiological testing (OR, 1.79; 95% CI, 1.15-2.73; P = 0.010) were independent predictors for inappropriate antibiotic prescribing. CONCLUSION: A considerable number of antimicrobial agents are administered to patients with chronic or acute illnesses nearing their end-of-life, a high proportion of which are prescribed inappropriately. Consultation with an infectious disease specialist, in addition to an antimicrobial stewardship program, may be necessary to induce the optimal use of antibiotics.

Antibiotic Susceptibility Surveillance in the Punjab Province of Pakistan: Findings and Implications.

Background and Objectives: The increase in antimicrobial resistance (AMR) across countries has seriously impacted the effective management of infectious diseases, with subsequent impact on morbidity, mortality and costs. This includes Pakistan. Antimicrobial surveillance activities should be mandatory to continually assess the extent of multidrug-resistant bacteria and the implications for future empiric prescribing. The objective of this retrospective observational study was to monitor the susceptibility pattern of microbes in Pakistan. Materials and Methods: Clinical samples from seven laboratories in Punjab, Pakistan were collected between January 2018 and April 2019, with Punjab being the most populous province in Pakistan. The isolates were identified and their antimicrobial susceptibility was tested using the Kirby-Bauer disc diffusion assay and micro broth dilution methods. The antibiotics assessed were those typically prescribed in Pakistan. Results: In total, 2523 bacterial cultural reports were studied. The most frequently isolated pathogens were Staphylococcus aureus (866, 34.3%), followed by Escherichia coli (814, 32.2%), Pseudomonas aeruginosa (454, 18.0%) and Klebsiella pneumoniae (269, 10.7%). Most pathogens were isolated from pus (1464, 58.0%), followed by urine (718, 28.5%), blood (164, 6.5%) and sputum (81, 3.2%). Conclusions: The findings suggest that current antimicrobial options are severally restricted in Pakistan due to the emergence of multidrug-resistant pathogens. This calls for urgent actions including initiating antimicrobial stewardship programs to enhance prudent prescribing of antibiotics. This includes agreeing on appropriate empiric therapy as part of agreed guidelines, in line with the WHO EML and AWaRe book, whilst awaiting culture reports. This is alongside other measures to reduce inappropriate antimicrobial prescribing and reverse the threat of rising AMR.

A Narrative Review of Recent Antibiotic Prescribing Practices in Ambulatory Care in Tanzania: Findings and Implications.

Background and objectives: There are concerns with the current prescribing practices of antibiotics in ambulatory care in Tanzania, including both the public and private sectors. These concerns need to be addressed as part of the national action plan (NAP) of Tanzania to reduce rising antimicrobial resistance (AMR) rates. Issues and concerns include high rates of prescribing of antibiotics for essentially self-limiting conditions. Consequently, there is a need to address this. As a result, the aims of this narrative review were to comprehensively summarize antibiotic utilization patterns particularly in ambulatory care and their rationale in Tanzania and to suggest ways forward to improve future prescribing practices. Materials and Methods: We undertook a narrative review of recently published studies and subsequently documented potential activities to improve future prescribing practices. Potential activities included instigating quality indicators and antimicrobial stewardship programs (ASPs). Results: Published studies have shown that antibiotics are being excessively prescribed in ambulatory care in Tanzania, in up to 95% to 96.3% of presenting cases depending on the sector. This is despite concerns with their appropriateness. High rates of antibiotic prescribing are not helped by variable adherence to current treatment guidelines. There have also been concerns with extensive prescribing of 'Watch' antibiotics in the private sector. Overall, the majority of antibiotics prescribed across the sectors, albeit inappropriately, were typically from the 'Access' group of antibiotics in the AWaRe (Access/Watch/Reserve) classification rather than 'Watch' antibiotics to limit AMR. The inappropriate prescribing of antibiotics in ambulatory care is linked to current knowledge regarding antibiotics, AMR, and ASPs among both prescribers and patients. Recommended activities for the future include improved education for all groups, the instigation of updated quality indicators, and the regular monitoring of prescribing practices against agreed-upon guidelines and indicators. Education for healthcare professionals on ASPs should start at undergraduate level and continue post qualification. Community advocacy on the rational use of antibiotics should also include social media activities to dispel misinformation. Conclusion: The quality of current prescribing practices of antibiotics in ambulatory care is sub-optimal in Tanzania. This needs to be urgently addressed.

The Impact of a National Antimicrobial Stewardship Program on Antibiotic Prescribing in Primary Care: An Interrupted Time Series Analysis.

BACKGROUND: The Quality Premium was introduced in 2015 to financially reward local commissioners of healthcare in England for targeted reductions in antibiotic prescribing in primary care. METHODS: We used a national antibiotic prescribing dataset from April 2013 until February 2017 to examine the number of antibiotic items prescribed, the total number of antibiotic items prescribed per STAR-PU (specific therapeutic group age/sex-related prescribing units), the number of broad-spectrum antibiotic items prescribed, and broad-spectrum antibiotic items prescribed, expressed as a percentage of the total number of antibiotic items. To evaluate the impact of the Quality Premium on antibiotic prescribing, we used a segmented regression analysis of interrupted time series data. RESULTS: During the study period, over 140 million antibiotic items were prescribed in primary care. Following the introduction of the Quality Premium, antibiotic items prescribed decreased by 8.2%, representing 5933563 fewer antibiotic items prescribed during the 23 post-intervention months, as compared with the expected numbers based on the trend in the pre-intervention period. After adjusting for the age and sex distribution in the population, the segmented regression model also showed a significant relative decrease in antibiotic items prescribed per STAR-PU. A similar effect was found for broad-spectrum antibiotics (comprising 10.1% of total antibiotic prescribing), with an 18.9% reduction in prescribing. CONCLUSIONS: This study shows that the introduction of financial incentives for local commissioners of healthcare to improve the quality of prescribing was associated with a significant reduction in both total and broad-spectrum antibiotic prescribing in primary care in England.

An Assessment of Potential Unintended Consequences Following a National Antimicrobial Stewardship Program in England: An Interrupted Time Series Analysis.

BACKGROUND: The "Quality Premium" (QP) introduced in England in 2015 aimed to financially reward local healthcare commissioners for targeted reductions in primary care antibiotic prescribing. We aimed to evaluate possible unintended clinical outcomes related to this QP. METHODS: Using Clinical Practice Research Datalink and Hospital Episode Statistics datasets, we examined general practitioner (GP) consultations (visits) and emergency hospital admissions related to a series of predefined conditions of unintended consequences of reduced prescribing. Monthly age- and sex-standardized rates were calculated using a direct method of standardization. We used segmented regression analysis of interrupted time series to evaluate the impact of the QP on seasonally adjusted outcome rates. RESULTS: We identified 27334 GP consultations and >5 million emergency hospital admissions with predefined conditions. There was no evidence that the QP was associated with changes in GP consultation and hospital admission rates for the selected conditions combined. However, when each condition was considered separately, a significant increase in hospital admission rates was noted for quinsy, and significant decreases were seen for hospital-acquired pneumonia, scarlet fever, pyelonephritis, and complicated urinary tract conditions. A significant decrease in GP consultation rates was estimated for empyema and scarlet fever. No significant changes were observed for other conditions. CONCLUSIONS: Findings from this study show that overall there was no significant association between the intervention and unintended clinical consequences, with the exception of a few specific conditions, most of which could be explained through other parallel policy changes or should be interpreted with caution due to small numbers.

Health care providers' perceptions regarding antimicrobial stewardship programs (AMS) implementation-facilitators and challenges: a cross-sectional study in the Eastern province of Saudi Arabia.

BACKGROUND: Infections result from invasions of an organism into body tissues leading to diseases and complications that might eventually lead to death. Inappropriate use of antimicrobials has led to development of antimicrobial resistance (AMR) which has been associated with increased mortality, morbidity and health costs. Antimicrobial stewardship (AMS) programs are designed to ensure appropriate selections of an effective antimicrobial drugs and optimizing antibiotic use to minimize antibiotic resistance by implementing certain policies, strategies and guidelines. The aim of this study was to investigate practitioners' perceptions regarding AMS implementation and to identify challenges and facilitators of these programs execution. METHODS: Cross-sectional study among health care providers in Eastern province of Saudi Arabia Hospitals. The data was collected using a survey including questions about demographic data and information about clinicians' (physicians, pharmacists and nurses) previous experience with AMS and prescribing of antibiotics, the level of knowledge and attitudes regarding AMS programs' implementation. RESULTS: More than 50% of clinicians (N = 184) reported lack of awareness of AMS programs and their components, whereas 71.2% do not have previous AMS experience. The majority of clinicians (72.3%) noticed increasing number of AMR infections over the past 5 years and (69.6%) were involved in care of patients with an antibiotic-resistant infection. Around 77.2% of respondents reported that formulary management can be helpful for AMS practice and majority of respondents (79.9%) reported that the availability of pathogens and antimicrobial susceptibility testing can be helpful for AMS. Major barriers to AMS implementation identified were lack of internal policy/guidelines and specialized AMS information resources. Lack of administrative awareness about AMS programs; lack of personnel, time limitation, limited training opportunities, lack of confidence, financial issue or limited funding and lack of specialized AMS information resources were also reported 65.8%, 62.5%, 60.9%, 73.9%, 50%, 54.3 and 74.5%, respectively. CONCLUSION: Our study identified comprehensive education and training needs for health care providers about AMS programs. Furthermore, it appears that internal policy and guidelines need revision to ensure that the health care providers work consistently with AMS. Future research must focus on the benefit of implementing AMS as many hospitals are not implementing AMS as revealed by the clinicians. We recommend policy makers and concerned health authorities to consider the study findings into account to optimize AMS implementation.

Long-Term Impact of an Educational Antimicrobial Stewardship Program on Hospital-Acquired Candidemia and Multidrug-Resistant Bloodstream Infections: A Quasi-Experimental Study of Interrupted Time-Series Analysis.

BACKGROUND: The global crisis of bacterial resistance urges the scientific community to implement intervention programs in healthcare facilities to promote an appropriate use of antibiotics. However, the clinical benefits or the impact on resistance of these interventions has not been definitively proved. METHODS: We designed a quasi-experimental intervention study with an interrupted time-series analysis. A multidisciplinary team conducted a multifaceted educational intervention in our tertiary-care hospital over a 5-year period. The main activity of the program consisted of peer-to-peer educational interviews between counselors and prescribers from all departments to reinforce the principles of the proper use of antibiotics. We assessed antibiotic consumption, incidence density of Candida and multidrug-resistant (MDR) bacteria bloodstream infections (BSIs) and their crude death rate per 1000 occupied bed days (OBDs). RESULTS: A quick and intense reduction in antibiotic consumption occurred 6 months after the implementation of the intervention (change in level, -216.8 defined daily doses per 1000 OBDs; 95% confidence interval, -347.5 to -86.1), and was sustained during subsequent years (average reduction, -19,9%). In addition, the increasing trend observed in the preintervention period for the incidence density of candidemia and MDR BSI (+0.018 cases per 1000 OBDs per quarter; 95% confidence interval, -.003 to .039) reverted toward a decreasing trend of -0.130 per quarter (change in slope, -0.029; -.051 to -.008), and so did the mortality rate (change in slope, -0.015; -.021 to -.008). CONCLUSIONS: This education-based antimicrobial stewardship program was effective in decreasing the incidence and mortality rate of hospital-acquired candidemia and MDR BSI through sustained reduction in antibiotic use.

Cost Analysis of Implementing Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry Plus Real-Time Antimicrobial Stewardship Intervention for Bloodstream Infections.

Studies evaluating rapid diagnostic testing plus stewardship intervention have consistently demonstrated improved clinical outcomes for patients with bloodstream infections. However, the cost of implementing new rapid diagnostic testing can be significant, and such testing usually does not generate additional revenue. There are minimal data evaluating the impact of adding matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for rapid organism identification and dedicating pharmacy stewardship personnel time on the total hospital costs. A cost analysis was performed utilizing patient data generated from the hospital cost accounting system and included additional costs of MALDI-TOF equipment, supplies and personnel, and dedicated pharmacist time for blood culture review and of making interventions to antimicrobial therapy. The cost analysis was performed from a hospital perspective for 3-month blocks before and after implementation of MALDI-TOF plus stewardship intervention. A total of 480 patients with bloodstream infections were included in the analysis: 247 in the preintervention group and 233 in the intervention group. Thirty-day mortality was significantly improved in the intervention group (12% versus 21%, P < 0.01), and the mean length of stay was reduced, although the difference was not statistically significant (13.0 ± 16.5 days versus 14.2 ± 16.7 days, P = 0.44). The total hospital cost per bloodstream infection was lower in the intervention group ($42,580 versus $45,019). Intensive care unit cost per bloodstream infection accounted for the largest share of the total costs in each group and was also lower in the intervention group ($10,833 versus $13,727). Implementing MALDI-TOF plus stewardship review and intervention decreased mortality for patients with bloodstream infections. Despite the additional costs of implementing MALDI-TOF and of dedicating pharmacy stewardship personnel time to interventions, the total hospital costs decreased by $2,439 per bloodstream infection, for an approximate annual cost savings of $2.34 million.

Evaluation of Hospital Antimicrobial Stewardship Programs: Implementation, Process, Impact, and Outcomes, Review of Systematic Reviews.

Antimicrobial Stewardship Programs (ASP) were introduced in healthcare as a public health priority to promote appropriate prescribing of antimicrobials, to reduce adverse events related to antimicrobials, as well as to control the escalating challenges of antimicrobial resistance. To deliver aimed outcome objectives, ASPs involve multiple connected implementation process measures. A systematic review was conducted to evaluate both concepts of ASPs. Guided by PRISMA frames, published systematic reviews (SR) focusing on ASPs restricted to secondary and tertiary healthcare were evaluated over the past 10 years involving all age groups. Out of 265 identified SR studies, 63 met the inclusion criteria. The majority were conducted in Europe and North America, with limited studies from other regions. In the reviewed studies, all age groups were examined, although they were conducted mainly on adults when compared to children and infants. Both process and outcomes measures of ASPs were examined equally and simultaneously through 25 different concepts, dominated by efficacy, antimicrobial resistance, and economic impact, while information technology as well as role of pharmacy and behavioral factors were equally examined. The main broad conclusions from the review were that, across the globe, ASPs demonstrated effectiveness, proved efficacy, and confirmed efficiency, while focused evaluation advocated that developed countries should target medium- and small-sized hospitals while developing countries should continue rolling ASPs across healthcare facilities. Additionally, the future of ASPs should focus on embracing evolving information technology to bridge the gaps in knowledge, skills, and attitude, as well as to enhance appropriate decision making.

Assessment of De-Escalation of Empirical Antimicrobial Therapy in Medical Wards with Recognized Prevalence of Multi-Drug-Resistant Pathogens: A Multicenter Prospective Cohort Study in Non-ICU Patients with Microbiologically Documented Infection.

Antimicrobial resistance poses a major threat to human health worldwide and the implementation of antimicrobial stewardship programs (ASPs), including antimicrobial de-escalation (ADE), is a multifaceted tool for minimizing unnecessary or inappropriate antibiotic exposure. This was a prospective observational study of 142 non-Intensive Care Unit (ICU) patients with microbiologically documented infection who were initially administered empirical antimicrobial therapy and admitted to the medical wards of 6 tertiary-care hospitals in Greece from January 2017 to December 2018. Patients were divided into two groups, the ADE and non-ADE group, based on whether ADE was applied or not, respectively. Exploratory end-points were ADE feasibility, safety and efficacy. ADE was applied in 76 patients at a median time of 4 days (IQR: 3, 5). An increased likelihood of ADE was observed in patients with urinary tract (OR: 10.04, 95% CI: 2.91, 34.57; p < 0.001), skin and soft tissue (OR: 16.28, 95% CI: 1.68, 158.08; p = 0.016) and bloodstream infections (OR: 2.52, 95% CI: 1, 6.36; p = 0.05). Factors significantly associated with higher rates of ADE were clarithromycin administration, diagnosis of urinary tract infection (UTI), isolation of E. coli, age and symptoms type on admission. Mortality was lower in the ADE group (18.4% vs. 30.3% p < 0.1) and ADE was not significantly associated with the probability of death (p = 0.432). ADE was associated with favorable clinical outcomes and can be performed even in settings with high prevalence of multi-drug resistant (MDR) pathogens without compromising safety.

Prospective Audit and Feedback for Antimicrobial Treatment of Patients Receiving Renal Replacement Therapy in Community-Based University Hospitals: A before-and-after Study.

In South Korea, because of manpower and budgetary limitations, antimicrobial stewardship programs have relied on preauthorization. This study analyzed the impact of a prospective audit and feedback (PAF) program targeting inpatients undergoing intermittent hemodialysis or continuous renal replacement therapy, which was implemented at two community-based university hospitals. During three years of PAF, 27,906 antimicrobial prescriptions were reviewed, with 622 (2.2%) interventions. The mean incidence density per 1000 patient days of multidrug-resistant organisms, except for carbapenem-resistant Acinetobacter baumannii, decreased in the study population, whereas it increased among inpatients. Multivariable Poisson regression analysis revealed that after PAF, the incidences of vancomycin-resistant Enterococcus and mortality decreased (incidence risk ratio, 95% confidence interval: 0.53, 0.31-0.93 and 0.70, 0.55-0.90, respectively). Notably, after PAF, incorrect antimicrobial dosing rates significantly decreased (tau -0.244; p = 0.02). However, the incidences of other multidrug-resistant organisms, Clostridioides difficile, length of stay, and readmission did not significantly change. This study shows that in patients undergoing intermittent hemodialysis or continuous renal replacement, targeted PAF can significantly reduce multidrug-resistant organism rates and all-cause hospital mortality, despite limited resources. Furthermore, it can improve antimicrobial dosage accuracy.

Mobile Colistin-Resistant Genes mcr-1, mcr-2, and mcr-3 Identified in Diarrheal Pathogens among Infants, Children, and Adults in Bangladesh: Implications for the Future.

Colistin is a last-resort antimicrobial for treating multidrug-resistant Gram-negative bacteria. Phenotypic colistin resistance is highly associated with plasmid-mediated mobile colistin resistance (mcr) genes. mcr-bearing Enterobacteriaceae have been detected in many countries, with the emergence of colistin-resistant pathogens a global concern. This study assessed the distribution of mcr-1, mcr-2, mcr-3, mcr-4, and mcr-5 genes with phenotypic colistin resistance in isolates from diarrheal infants and children in Bangladesh. Bacteria were identified using the API-20E biochemical panel and 16s rDNA gene sequencing. Polymerase chain reactions detected mcr gene variants in the isolates. Their susceptibilities to colistin were determined by agar dilution and E-test by minimal inhibitory concentration (MIC) measurements. Over 31.6% (71/225) of isolates showed colistin resistance according to agar dilution assessment (MIC > 2 µg/mL). Overall, 15.5% of isolates carried mcr genes (7, mcr-1; 17, mcr-2; 13, and mcr-3, with co-occurrence occurring in two isolates). Clinical breakout MIC values (≥4 µg/mL) were associated with 91.3% of mcr-positive isolates. The mcr-positive pathogens included twenty Escherichia spp., five Shigella flexneri, five Citrobacter spp., two Klebsiella pneumoniae, and three Pseudomonas parafulva. The mcr-genes appeared to be significantly associated with phenotypic colistin resistance phenomena (p = 0.000), with 100% colistin-resistant isolates showing MDR phenomena. The age and sex of patients showed no significant association with detected mcr variants. Overall, mcr-associated colistin-resistant bacteria have emerged in Bangladesh, which warrants further research to determine their spread and instigate activities to reduce resistance.

Days of Antibiotic Spectrum Coverage (DASC) as a Metric for Evaluating the Impact of Prospective Audit and Feedback (PAF) against Long-Term Broad-Spectrum Antibiotic Use.

The present study aimed to evaluate the impact of prospective audit and feedback (PAF) on the use of inpatient broad-spectrum antibiotics for more than 10 days using days of therapy (DOT) and a novel metric called days of antibiotic spectrum coverage (DASC) to assess whether the antimicrobial spectrum was narrowed. Conducted at Aichi Medical University Hospital in Japan, the study compared a six-month baseline period (April to September 2022) with a six-month intervention period (April to September 2023). The primary outcome measures were changes in DOT/patient and DASC/patient for broad-spectrum antibiotics. Propensity score matching was performed between two periods and a total of 172 patients were included in the study (pre-intervention, n = 86; intervention, n = 86). The DASC/patient of broad-spectrum antibiotics was statistically decreased in the intervention period compared to that in the baseline period (153.3 vs. 122.7, p < 0.05). Additionally, our PAF intervention led to a switch to narrow-spectrum antimicrobial therapy without increasing all-cause 30-day mortality (5.8% vs. 5.8%, p = 1.0). However, the DOT/patient, DASC/patient, and DASC/DOT of all antimicrobials were not significantly changed. Our study concluded that we should reconsider the timing of PAF intervention by evaluating the effort of PAF by using DOT and DASC.

Resistance and Co-Resistance of Metallo-Beta-Lactamase Genes in Diarrheal and Urinary-Tract Pathogens in Bangladesh.

Carbapenems are the antibiotics of choice for treating multidrug-resistant bacterial infections. Metallo-ß-lactamases (MBLs) are carbapenemases capable of hydrolyzing nearly all therapeutically available beta-lactam antibiotics. Consequently, this research assessed the distribution of two MBL genes and three ß-lactamases and their associated phenotypic resistance in diarrheal and urinary-tract infections (UTIs) to guide future policies. Samples were collected through a cross-sectional study, and ß-lactamase genes were detected via PCR. A total of 228 diarrheal bacteria were isolated from 240 samples. The most predominant pathogens were Escherichia coli (32%) and Klebsiella spp. (7%). Phenotypic resistance to amoxicillin-clavulanic acid, aztreonam, cefuroxime, cefixime, cefepime, imipenem, meropenem, gentamicin, netilmicin, and amikacin was 50.4%, 65.6%, 66.8%, 80.5%, 54.4%, 41.6%, 25.7%, 41.2%, 37.2%, and 42.9%, respectively. A total of 142 UTI pathogens were identified from 150 urine samples. Klebsiella spp. (39%) and Escherichia coli (24%) were the major pathogens isolated. Phenotypic resistance to amoxicillin-clavulanic acid, aztreonam, cefuroxime, cefixime, cefepime, imipenem, meropenem, gentamicin, netilmicin, and amikacin was 93.7%, 75.0%, 91.5%, 93.7%, 88.0%, 72.5%, 13.6%, 44.4%, 71.1%, and 43%, respectively. Twenty-four diarrheal isolates carried blaNDM-1 or blaVIM genes. The overall MBL gene prevalence was 10.5%. Thirty-six UTI pathogens carried either blaNDM-1 or blaVIM genes (25.4%). Seven isolates carried both blaNDM-1 and blaVIM genes. MBL genes were strongly associated with phenotypic carbapenem and other ß-lactam antibiotic resistance. blaOXA imparted significantly higher phenotypic resistance to ß-lactam antibiotics. Active surveillance and stewardship programs are urgently needed to reduce carbapenem resistance in Bangladesh.

Leveraging Large Data, Statistics, and Machine Learning to Predict the Emergence of Resistant E. coli Infections.

Drug-resistant Gram-negative bacterial infections, on average, increase the length of stay (LOS) in U.S. hospitals by 5 days, translating to approximately $15,000 per patient. We used statistical and machine-learning models to explore the relationship between antibiotic usage and antibiotic resistance over time and to predict the clinical and financial costs associated with resistant E. coli infections. We acquired data on antibiotic utilization and the resistance/sensitivity of 4776 microbial cultures at a Kaiser Permanente facility from April 2013 to December 2019. The ARIMA (autoregressive integrated moving average), neural networks, and random forest time series algorithms were employed to model antibiotic resistance trends. The models' performance was evaluated using mean absolute error (MAE) and root mean squared error (RMSE). The best performing model was then used to predict antibiotic resistance rates for the year 2020. The ARIMA model with cefazolin, followed by the one with cephalexin, provided the lowest RMSE and MAE values without signs of overfitting across training and test datasets. The study showed that reducing cefazolin usage could decrease the rate of resistant E. coli infections. Although piperacillin/tazobactam did not perform as well as cefazolin in our time series models, it performed reasonably well and, due to its broad spectrum, might be a practical target for interventions in antimicrobial stewardship programs (ASPs), at least for this particular facility. While a more generalized model could be developed with data from multiple facilities, this study acts as a framework for ASP clinicians to adopt statistical and machine-learning approaches, using region-specific data to make effective interventions.

Antimicrobial Stewardship: A Correct Management to Reduce Sepsis in NICU Settings.

The discovery of antimicrobial drugs has led to a significant increase in survival from infections; however, they are very often prescribed and administered, even when their use is not necessary and appropriate. Newborns are particularly exposed to infections due to the poor effectiveness and the immaturity of their immune systems. For this reason, in Neonatal Intensive Care Units (NICUs), the use of antimicrobial drugs is often decisive and life-saving, and it must be started promptly to ensure its effectiveness in consideration of the possible rapid evolution of the infection towards sepsis. Nevertheless, the misuse of antibiotics in the neonatal period leads not only to an increase in the development and wide spreading of antimicrobial resistance (AMR) but it is also associated with various short-term (e.g., alterations of the microbiota) and long-term (e.g., increased risk of allergic disease and obesity) effects. It appears fundamental to use antibiotics only when strictly necessary; specific decision-making algorithms and electronic calculators can help limit the use of unnecessary antibiotic drugs. The aim of this narrative review is to summarize the right balance between the risks and benefits of antimicrobial therapy in NICUs; for this purpose, specific Antimicrobial Stewardship Programs (ASPs) in neonatal care and the creation of a specific antimicrobial stewardship team are requested.

Evaluation of new antimicrobials for the hospital formulary. Policies restricting antibiotic use in hospitals.

In Spain, the inclusion of new antibiotics in hospital formularies is performed by the Infection Policy Committee or the Pharmacy and Therapeutic Committee, although now the decision is moving to a regional level. Criteria for the evaluation of new drugs include efficacy, safety and cost. For antimicrobial drugs evaluation it is necessary to consider local sensibility and impact in bacterial resistance to determinate the therapeutic positioning. There is compelling evidence that the use of antibiotics is associated with increasing bacterial resistance, and a great number of antibiotics are used incorrectly. In order to decrease the inappropriate use of antibiotics, several approaches have been proposed. Limiting the use of antimicrobials through formulary restrictions, often aimed at drugs with a specific resistance profile, shows benefits in improving antimicrobial susceptibilities and decreasing colonization by drug-resistant organisms. However, the restriction of one agent may result in the increased utilization of other agents. By using antibiotic cycling, the amount of antibiotics is maintained below the threshold where bacterial resistance develops, thus preserving highly efficient antibiotics. Unfortunately, cumulative evidence to date suggests that antibiotic cycling has limited efficacy in preventing antibiotic resistance. Finally, although there is still little clinical evidence available on antibiotic heterogeneity, the use of most of the existing antimicrobial classes could limit the emergence of resistance. This review summarizes information regarding antibiotic evaluation and available restrictive strategies to limit the use of antibiotics at hospitals with the aim of curtailing increasing antibiotic resistance.

Carbapenem Use in the Last Days of Life: A Nationwide Korean Study.

The appropriate use of carbapenem is a critical concern for patient safety and public health, and is a national priority. We investigated the nationwide status of carbapenem prescription in patients within their last 14 days of life to guide judicious-use protocols from the previous study comprised of 1350 decedents. Carbapenem use was universally controlled through computerised authorisation system at all centres during the study period. Carbapenem prescribing patterns and their optimality were evaluated. A total of 1201 patients received antimicrobial agents within the last two weeks of their lives, of whom 533 (44.4%) received at least one carbapenem. The median carbapenem treatment duration was seven days. Of the 533 patients receiving carbapenems, 510 (95.7%) patients had microbiological samples drawn and 196 (36.8%) yielded carbapenem-resistant pathogens. A total of 200 (37.5%) patients were referred to infectious disease (ID) specialists. Of the 333 patients (62.5%) who did not have ID consultations, 194 (58.2%) were assessed as "not optimal", 79 (23.7%) required escalation, 100 (30.0%) required de-escalation, and 15 (4.5%) were discontinued. Notwithstanding the existing antibiotic restriction program system, carbapenems are commonly prescribed to patients in their last days of life.