Narrow-spectrum Antibiotics Research Articles

Exposure to antibiotics and risk of latent autoimmune diabetes in adults and type 2 diabetes: results from a Swedish case-control study (ESTRID) and the Norwegian HUNT study.

Some studies find an increased risk of type 1 diabetes in children exposed to antibiotics. We investigated if exposure to antibiotics increases the risk of latent autoimmune diabetes in adults (LADA) and type 2 diabetes. We used data from a Swedish case-control study (Epidemiological Study of Risk Factors for LADA and Type 2 Diabetes [ESTRID]: LADA, n=597; type 2 diabetes, n=2065; control participants matched on participation time, n=2386) and a case-control study nested within the Norwegian Trøndelag Health Study (HUNT) (n=82/1279/2050). Anatomical Therapeutic Chemical (ATC) codes indicating antibiotic dispensations were retrieved from the Swedish National Prescribed Drug Register and Norwegian Prescription Database. Multivariable adjusted ORs with 95% CIs were estimated by conditional logistic regression and pooled using fixed-effects inverse-variance weighting. We observed no increased risk of LADA with exposure to antibiotics up to 1 year (ORpooled 1.15, 95% CI 0.93, 1.41) or 1-5 years (ORpooled 0.98, 95% CI 0.80, 1.20) prior to diagnosis/matching for one or more vs no dispensation of any type of antibiotic. An increased risk was observed for one or more vs no dispensations of narrow-spectrum antibiotics, but not broad-spectrum antibiotics, 6-10 years prior to LADA diagnosis (ORpooled 1.39, 95% CI 1.01, 1.91), which was driven by the Swedish data. There was little evidence of an increased risk of type 2 diabetes associated with antibiotic exposure 1-10 years prior to diagnosis. We found no evidence that exposure to broad-spectrum antibiotics up to 10 years prior to diagnosis increases the risk of LADA. There was some indication of increased LADA risk with exposure to narrow-spectrum antibiotics, which warrants further investigation.

Antibiotic spectrum coverage scoring as a potential metric for evaluating the antimicrobial stewardship team activity: a single-center study.

Days of antibiotic spectrum coverage (days of ASC: DASC) is a metric for antibiotic usage calculated by ASC scores for spectrum and addresses limitations of days of therapy (DOT), which does not include spectrum. This study aims to investigate whether ASC-related metrics offer different aspects compared to aggregated DOT for all antibiotics (DOTtotal) and to assess their correlation in evaluating the impact of antimicrobial stewardship team (AST) programs. Retrospective. A single center within an 845-bed hospital. Trends in DOTtotal, DASC, and the DASC/DOT ratio, representing the average spectrum coverage per therapy day, were analyzed pre- and post-AST programs (April 2018) from January 2015 to December 2023, using interrupted time series analysis. Independent of the DASC/DOT, we also advocated ASC-stratified DOT (ASDOT), which facilitates comprehensive evaluation of DOT across ASC scores of <6, 6-10, and >10, representing narrow-, intermediate-, and broad-spectrum antibiotics. Among inpatients, AST programs significantly moderated the increasing trends of these metrics. Specifically, although the rates of increase in DOTtotal and DASC were slowed or plateaued, the DASC/DOT ratio decreased (P < 0.001). ASDOT metrics revealed a decrease and subsequent plateau in DOTtotal for the broad- and intermediate-spectrum antibiotics, with an increase observed for the narrow-spectrum antibiotics (P < 0.001 for each). DASC did not provide additional insights in the outpatient's population. The study demonstrates that ASC-related metrics may yield different and useful conclusions about the effectiveness of AST programs for inpatients.

Antibiotic Appropriateness for Urinary Tract Infections in Children.

We examined local prescribing patterns across the entire treatment course for children treated for uncomplicated urinary tract infection (UTI) to determine opportunities for antibiotic stewardship initiatives. We conducted a retrospective review of emergency department and inpatient encounters for febrile and afebrile UTI in a children's hospital from 2021 to 2022. An antibiotic spectrum ranking was established, and providers' choices were assessed for appropriateness on the basis of the individuals' urine culture (UCx). Groups were stratified by fever presence and compared using χ2, Fisher's exact, and Mann-Whitney U tests. Of 172 encounters (83% emergency department), 99 (58%) had a positive UCx. Eighty (80%) grew Escherichia coli, with 67 (84%) being susceptible to cefazolin (minimum inhibitory concentration ≤16 mg/L). There were 229 antibiotic regimens and 39 (17%) were appropriate. Inappropriate antibiotic choices included unnecessary use of broad-spectrum antibiotics and misdiagnosed UTI. Grouping by encounter, at least 1 dose of a third cephalosporin was given in 51% of encounters, and 80% of these received it unnecessarily because of UTI misdiagnosis or suitability of a narrower-spectrum antibiotic. The median prescribed antibiotic duration was 7 days (interquartile range 7-10). Of 73 encounters with UCx growing mixed flora or a nonuropathogen, only 29 (40%) had antibiotics discontinued. Confirmed UTI was associated with fever and nitrite positivity. Our study revealed high prevalence of inappropriate antibiotics, particularly unnecessary prescribing of third cephalosporin, prescriptions not supported by laboratory data, and prolonged treatment courses. Our results identify factors that can be used to support UTI treatment pathways and ensure antibiotic stewardship.

Empiric gram-negative antibiotics usage among critically ill patients across 13 ICUs of Nepal: A retrospective cohort study

Background This study aims to investigate the associations between patient characteristics and the receipt of empiric broad-spectrum gram-negative antimicrobials among adult patients admitted to ICUs in Nepal. Methods A retrospective cohort study was conducted in 13 ICUs in Nepal between January 1st, 2020, and December 31st, 2022. Empiric antibiotic use was defined as receiving gram-negative antibiotics within the first two days of ICU admission without evidence of infection from culture. Patient characteristics between patients receiving narrow-spectrum antibiotics and broad-spectrum gram-negative antibiotics were compared. Continuous variables were compared using mean and standard deviation, with mean differences and 95% confidence intervals calculated. Categorical variables were compared using the chi-square test. A multi-level multivariable regression model assessed the relationship between selected variables and broad-spectrum antibiotic usage, treating admitting ICU as a random factor. Results Among 12,349 eligible patients, 8720 (70.6%) received Empiric gram-negative antibiotics. Of those, 3240 (37.15%) received empiric narrow-spectrum gram-negative antibiotics, and 5480 (62.8%) received Empiric broad-spectrum gram-negative antibiotics. Patients receiving broad-spectrum gram-negative antibiotics were older (57.4 vs 53.8 yrs); had higher mean heart rates (97.3 vs 89.5 bpm), respiratory rates (24 vs 21.9), a fraction of inspired oxygen ( 50% vs 40%), blood sugar levels (163.4 vs 153.9 mg/dl), total leucocyte counts (12,685 vs 10,647 cells/cu mm) and serum creatinine (2.06 vs 1.03 umol/l) compared to narrow spectrum antibiotics. Similarly, patients receiving broad-spectrum gram-negative antibiotics had lower systolic blood pressure (122.6 vs 126.5 mm Hg), partial pressure of oxygen (96.7 vs 105.3), and pH ( 7.33 vs 7.36) compared to narrow-spectrum antibiotics. On multivariable regression; patients with readmission, cardiac support, and mechanical ventilation were more likely to receive broad-spectrum antibiotics. Conclusion The rate of empiric broad-spectrum gram-negative antibiotics usage in intensive care units is significantly high and associated with features of increased severity of illness.

Adoption of clinical pharmacist roles in primary care: Longitudinal evidence from English general practice.

Over the last decade, the number of clinical pharmacists working within multidisciplinary teams in English general practice has expanded Aim: This study examines changes in quality of prescribing after the adoption of clinical pharmacists in English general practices. Two-way fixed effects regression was used to compare differences in prescribing indicators in general practices in England with and without pharmacists following implementation between September 2015 and December 2019 Results: Between September 2015 and December 2019, the proportion of practices employing a clinical pharmacist increased from 236/ 7,623 (3.10%) to 1,402/ 6,836 (20.51%). Clinical pharmacist implementation resulted in statistically significant reductions in total costs of medicines per 1,000 patients (-0.85% ,95% CI -1.50%, -0.21%), the total number of opioid prescriptions per 1,000 patients (- 1.06%, 95% CI -1.82%, -0.29%), and the average daily quantity (ADQs) of anxiolytics per 1,000 patients (-1.26%, 95% CI -2.40%, -0.12%). Clinical pharmacist implementation also resulted in reductions in the total number of prescriptions per 1,000 patients (-0.58%, 95% CI -1.30%, 0.13%), and the total number of antibiotic prescriptions per 1,000 patients (-0.51%, 95% CI -1.30%, 0.27%) that trended towards statistical significance. There were no statistically significant differences in the share of broad-spectrum versus narrow-spectrum antibiotics (0.02%, 95% CI -0.07%, 0.11%) and the oral morphine equivalence of high-dose opioids (>120mg per 24 hours) per 1,000 patients (1.19%, 95% CI -0.46%, 2.85%). Our analysis is limited by aggregate data at the practice-level but supports the hypothesis that clinical pharmacist implementation results in improvements in prescribing quality.

Novel Drug-like HsrA Inhibitors Exhibit Potent Narrow-Spectrum Antimicrobial Activities against Helicobacter pylori.

Helicobacter pylori infection constitutes a silent pandemic of global concern. In the last decades, the alarming increase in multidrug resistance evolved by this pathogen has led to a marked drop in the eradication rates of traditional therapies worldwide. By using a high-throughput screening strategy, in combination with in vitro DNA binding assays and antibacterial activity testing, we identified a battery of novel drug-like HsrA inhibitors with MIC values ranging from 0.031 to 4 mg/L against several antibiotic-resistant strains of H. pylori, and minor effects against both Gram-negative and Gram-positive species of human microbiota. The most potent anti-H. pylori candidate demonstrated a high therapeutic index, an additive effect in combination with metronidazole and clarithromycin as well as a strong antimicrobial action against Campylobacter jejuni, another clinically relevant pathogen of phylum Campylobacterota. Transcriptomic analysis suggests that the in vivo inhibition of HsrA triggers lethal global disturbances in H. pylori physiology including the arrest of protein biosynthesis, malfunction of respiratory chain, detriment in ATP generation, and oxidative stress. The novel drug-like HsrA inhibitors described here constitute valuable candidates to a new family of narrow-spectrum antibiotics that allow overcoming the current resistome, protecting from dysbiosis, and increasing therapeutic options for novel personalized treatments against H. pylori.

Antibiotic Prescribing Trends in Dentistry during Ten Years' Period-Croatian National Study.

Prescribing antibiotics is a regular part of daily dental practice. Antibiotics have a significant but a limited role in general dental practice due to the threat of emergence of antimicrobial resistance (AMR). As such, the aim of this study was to assess prescribing trends in dental antibiotics use from 2014-2023 in Croatia. Data on antibiotic prescribing practices for this study were provided by the Croatian Health Insurance Fund. The analysis included the number of prescriptions, packages, cost, and the World Health Organization's defined daily dose per 1000 inhabitants (DID) per day as an objective utilization for comparison. Over the 10-year period, dentists in Croatia prescribed an annual average of 357,875 antibiotic prescriptions, representing an annual average of 78.7% of all dental prescriptions. The most commonly prescribed antibiotic was the combination of amoxicillin and the beta-lactamase inhibitor clavulanic acid, which made up 58.54% of antibiotics and 46.1% of all dental prescriptions. This was followed by amoxicillin (12.61%), clindamycin (12.58%), and metronidazole (9.96%). The trend showed two discontinuations, the first for the pandemic years, and the second caused by disruption in amoxicillin production. The rise in the use of broad-spectrum antibiotics needs to be addressed and regulated to ensure patients and dentists understand that antibiotics are not a substitute for dental treatment. Dentists should always begin treatment with narrow-spectrum antibiotics regardless of possible exceptional circumstances.

Early clinical outcomes of two regimens of prophylactic antibiotics in cardiac surgical patients with delayed sternal closure.

Delayed sternal closure (DSC) can be a lifesaving approach for certain patients who have undergone cardiac surgery. The value of the type of prophylactic antibiotics in DSC is still debatable. To investigate clinical outcomes of different prophylactic antibiotic regimens in patients who had DSC after cardiac surgery. This was a retrospective observational single-center study. Fifty-three consecutive patients who underwent cardiac surgery and had an indication for DSC were included. Patients were subjected to two regimens of antibiotics: Narrow-spectrum and broad-spectrum regimens. The main outcome measures were length of hospital and intensive care unit (ICU) stay, duration of mechanical ventilation, and mortality. Of the 53 patients, 12 (22.6%) received narrow-spectrum antibiotics, and 41 (77.4%) received broad-spectrum antibiotics. The mean age was 59.0 ± 12.1 years, without significant differences between the groups. The mean duration of antibiotic use was significantly longer in the broad-spectrum than the narrow-spectrum group (11.9 ± 8.7 vs 3.4 ± 2.0 d , P < 0.001). The median duration of open chest was 3.0 (2.0-5.0) d for all patients, with no difference between groups (P = 0.146). The median duration of mechanical ventilation was significantly longer in the broad-spectrum group [60.0 (Δ interquartile range (IQR) 170.0) h vs 50.0 (ΔIQR 113.0) h, P = 0.047]. Similarly, the median length of stay for both ICU and hospital were significantly longer in the broad-spectrum group [7.5 (ΔIQR 10.0) d vs 5.0 (ΔIQR 5.0) d, P = 0.008] and [27.0 (ΔIQR 30.0) d vs 19.0 (ΔIQR 21.0) d, P = 0.031]. Five (9.8%) patients were readmitted to the ICU and 18 (34.6%) patients died without a difference between groups. Prophylactic broad-spectrum antibiotics did not improve clinical outcomes in patients with DSC post-cardiac surgery but was associated with longer ventilation duration, length of ICU and hospital stays vs narrow-spectrum antibiotics.

Early Antibiotic De-escalation in Patients With Severe Infections Due to Bloodstream Infection by Enterobacterales: A Post Hoc Analysis of a Prospective Multicentre Cohort

Data about antibiotic de-escalation in sepsis associated with the bloodstream and caused by Enterobacterales are scarce. The objectives of this study are to identify factors associated with early de-escalation and to analyse the impact of de-escalation on mortality in patients with Enterobacterales bloodstream infection (BSI) with a Sequential Organ Failure Assessment (SOFA) score ≥ 2. A prospective, multicentre cohort study was performed including episodes of BSI due to Enterobacterales and a SOFA score ≥ 2 who were receiving an active antipseudomonal β-lactam; the isolate should be susceptible to at least 1 narrower-spectrum antibiotic. Variables associated with de-escalation were identified using logistic binary regression. The association of de-escalation with 30-day mortality was investigated. Confounding was controlled by calculating a propensity score used as covariate, as matching variable, and for inverse probability treatment weighting. Of the 582 patients included, de-escalation was performed in 311 (53.4%). Neutropenia (adjusted odds ratio [aOR] = 0.37; 95% confidence interval [95% CI] = 0.18-0.75), central venous catheter (aOR = 0.52; 95% CI = 0.32-0.83), and extended-spectrum β-lactamase (ESBL)-producing isolate (aOR = 0.28; 95% CI = 0.17-0.48) were negatively associated with de-escalation, and urinary tract source was positively associated (aOR = 2.27; 95% CI = 1.56-3.33). The 30-day mortality was 6.8% (21 patients) in de-escalated patients and 14.4% (39) in not de-escalated patients (relative risk, 0.63; 95% CI = 0.44-0.89). In multivariate analysis including the propensity score, de-escalation was not associated with mortality (AOR = 0.98; 95% CI = 0.39-2.47) and was protective in the case of urinary or biliary tract source (AOR = 0.31, 95% CI = 0.09-1.06). Matched and inverse probability treatment weighting analysis showed similar results. These results suggest that early de-escalation from antipseudomonal β-lactams is safe in patients with Enterobacterales bacteremia and SOFA ≥ 2.

Variation in Antibiotic Prescription in High-Risk Febrile Neutropenia in Portuguese Hospitals.

Febrile neutropenia (FN) is a potentially severe entity, particularly in hemato-oncologic patients who have higher incidence of colonization with multidrug-resistant bacteria. Discrepancies among guidelines contribute to divergence in antimicrobial practices. Our objective was to assess the variation of practices in antimicrobial therapy in high-risk FN among Portuguese hematologists. We conducted a cross-sectional study through the implementation of an online survey, open to all clinical hematologists in the country. To characterize practice patterns regarding critical elements in FN management, three clinical vignettes were designed to describe typical situations where narrow-spectrum empiric antibiotics (vignette 1), short-course therapy (vignette 2) and de-escalation (vignette 3) could be performed. The remaining questions characterized clinical experience, department size, and differentiation and decision-making process regarding FN antibiotic therapy. The survey yielded 31 responses from 11 hospitals across four regions. All respondents opted for empiric narrow-spectrum antibiotics, 22.6% opted for short-course therapy (mostly senior specialists from larger settings) and 35.5% for de-escalation (mostly young specialists). Availability of an FN protocol seemed to favor both approaches. These findings should be complemented by qualitative assessments of barriers to best practices and should support the need for interventions to improve antibiotic use in febrile neutropenia.

The evolution of knowledge for treating Gram-negative bacterial infections.

Infections caused by nonprimarily pathogenic Gram-negative bacilli (GNB) have been increasingly reported from the second half of the 20th century to the present. This phenomenon has expanded during the antibiotic era and in the presence of immunodeficiency.Before the discovery of sulphonamides and penicillin G, infections caused by GNB were rare compared to Gram-positive infections. The advent of anticancer therapy, the expansion of surgical procedures, the use of corticosteroids, and the implantation of prosthetic materials, along with better control of Gram-positive infections, have promoted the current increase in GNB infections.GNB have similar antimicrobial targets to Gram-positive bacteria. However, only antibiotics that can penetrate the double membrane of GNB and remain in them for a sufficient duration have antibacterial activity against them. Sulphonamides and early penicillins had limited activity against GNB. Ampicillin and subsequent beta-lactams expanded their spectrum to treat GNB. Aminoglycosides may re-surge with less toxic drugs, as highly resistant to beta-lactams GNB rise. Polymyxins, tetracyclines, and fluoroquinolones are also used for GNB. Combinations with other agents may be needed in specific cases, such as in the central nervous system and prostate, where beta-lactams may have difficulty reaching the infection site.Alternatives to current treatments must be sought in the discovery of new drug families and therapies such as phage therapy combined with antibiotics. Narrower-spectrum immunosuppressive therapies and antibiotics, antimicrobials that minimally intervene with the human microbiota, and instant diagnostic methods are necessary to imagine a future where currently dominant bacteria in infectious pathology lose their preeminence.

Combination of High-Dose Daptomycin and Ceftriaxone for Cardiac Implantable Electronic Device Infections: A 10-Year Experience

PurposeCardiac implantable electronic device (CIED) infections are increasingly common. Gram-positive bacteria such as coagulase negative staphylococci and Staphylococcus aureus are the most commonly involved pathogens. The aim of this study was to describe the characteristics and outcome of patients with CIED infections who underwent device removal and were empirically treated with high dose (8–12 mg/kg daily) daptomycin (DAP) in combination with ceftriaxone (CRO). MethodsRetrospective, single center study including patients admitted at IRCCS San Raffaele Hospital (Milan, Italy), from June 2011 to June 2021, who underwent device removal for CIED infection and were empirically treated with DAP/CRO. FindingsOverall, 147 patients were included in this study. Median duration of therapy was 16 days (IQR 14–26). Empirical treatment with DAP/CRO was confirmed as definitive treatment in 140 patients (95.2%). In 7 (4.8%) patients DAP/CRO were discontinued according to the definite microbiological isolates: Corynebacterium spp. (4), Pseudomonas aeruginosa (2), Enterobacter cloacae (1). Ten patients (6.8%) underwent treatment simplification to narrow-spectrum antibiotics. One patient (0.6%) interrupted DAP-CRO due to pancytopenia.6-month follow-up was available for 123/147 patients (83.7%): 9 patients recurred with a CIED infection (7.3%), and 9 died (7.3%). ImplicationsIn our 10-year experience, high-dose DAP in combination with CRO represented a good option for empirical therapy of CIED infections. DAP-CRO combination was safe and effective, showing no significant drug-related adverse events and low rates of 6-month recurrence and mortality.

Modelling the implementation of narrow versus broader spectrum antibiotics in the empiric treatment of E. coli bacteraemia

The implementation of new antimicrobial resistance stewardship programs is crucial in optimizing antibiotic use. However, prescription choices can be difficult during empiric therapy; clinicians must balance the survival benefits of broader spectrum antibiotics with associated increases in resistance. The aim of this study was to evaluate the overall feasibility of switching to narrow spectrum antibiotics during the empiric treatment of E. coli bacteraemia by quantifying changes in resistance rates, antibiotic usage, and mortality using a deterministic state-transition model. Three unique model scenarios (A, B, and C), each representing a progressively broader spectrum empiric treatment regimen, were used to compare outcomes at 5 years. We show that the empiric use of the narrowest spectrum (first-line) antibiotics can lead to reductions in resistance to second-line antibiotics and the use of third-line antibiotics, but they also lead to increases in resistance to first-line therapy and higher mortality. Crucially, we find that shortening the duration of empiric and overall treatment, as well as reducing the baseline mortality rate, are important for increasing the feasibility of switching to narrow spectrum antibiotics in the empiric treatment of E. coli bacteraemia. We provide a flexible model design to investigate optimal treatment approaches for other bacterial infections.

Management of Clostridioides difficile infection: an Italian Delphi consensus.

Clostridioides difficile infection (CDI), a leading cause of nosocomial deaths, is a microbiota-mediated disease. As such, the use of broader spectrum antibiotics, such as vancomycin and metronidazole, can prime the gastrointestinal tract to become more prone to CDI recurrences. Fidaxomicin, a narrow-spectrum antibiotic, has been demonstrated to be superior in preventing recurrence and in preserving the intestinal microbiota; however, widespread employment worldwide has been hindered due to high acquisition costs. To integrate the currently available guidelines on the management of CDI and to shed light on the timeliest employment of fidaxomicin. An expert panel was gathered to obtain consensus using Delphi methodology on a series of statements regarding the management of CDI and on appropriate antibiotic use. Consensus was reached on 21 of the 25 statements addressing the management of CDI. Delphi methodology was used to achieve consensus on the management of CDI, on the identification of patients at risk of recurrences or severe infection, and on the most appropriate use of fidaxomicin, with the final aim of fostering clinical practice application of treatment algorithms proposed by previous guidelines, in absolute synergy. It could be an important tool to promote more appropriate and cost-effective CDI treatments in European settings with limited resources, like Italy.

Doctors' perception on the ethical use of AI-enabled clinical decision support systems for antibiotic prescribing recommendations in Singapore.

The increased utilization of Artificial intelligence (AI) in healthcare changes practice and introduces ethical implications for AI adoption in medicine. We assess medical doctors' ethical stance in situations that arise in adopting an AI-enabled Clinical Decision Support System (AI-CDSS) for antibiotic prescribing decision support in a healthcare institution in Singapore. We conducted in-depth interviews with 30 doctors of varying medical specialties and designations between October 2022 and January 2023. Our interview guide was anchored on the four pillars of medical ethics. We used clinical vignettes with the following hypothetical scenarios: (1) Using an antibiotic AI-enabled CDSS's recommendations for a tourist, (2) Uncertainty about the AI-CDSS's recommendation of a narrow-spectrum antibiotic vs. concerns about antimicrobial resistance, (3) Patient refusing the "best treatment" recommended by the AI-CDSS, (4) Data breach. More than half of the participants only realized that the AI-enabled CDSS could have misrepresented non-local populations after being probed to think about the AI-CDSS's data source. Regarding prescribing a broad- or narrow-spectrum antibiotic, most participants preferred to exercise their clinical judgment over the AI-enabled CDSS's recommendations in their patients' best interest. Two-thirds of participants prioritized beneficence over patient autonomy by convincing patients who refused the best practice treatment to accept it. Many were unaware of the implications of data breaches. The current position on the legal liability concerning the use of AI-enabled CDSS is unclear in relation to doctors, hospitals and CDSS providers. Having a comprehensive ethical legal and regulatory framework, perceived organizational support, and adequate knowledge of AI and ethics are essential for successfully implementing AI in healthcare.

Impact of COVID-19 pandemic on the utilization and quality of antibiotic use in the primary care setting in England, March 2019–March 2023: a segmented interrupted time series analysis of over 53 million individuals

ABSTRACT Background Amid the COVID-19 pandemic, we evaluated the short-term impact of COVID-19 on antibiotic use in primary care in England, focusing on both antibiotic quantity (overuse) and quality (misuse) of use. Research design and methods A population-based segmented interrupted analysis was applied on monthly dispensed antibiotics prescriptions using the Prescription Cost Analysis dataset (March/2019–March/2023). The quantity was assessed using number of items dispensed per 1000 inhabitants (NTI) and defined daily doses per 1000 inhabitants per day (DID), while quality was evaluated using WHO’s Access Watch Reserve (AWaRe) classification, the proportion of ‘4C’ antibiotics and the percentage of broad- to narrow-spectrum antibiotics. Results Findings indicate 8.6 (17.2%) and 0.4 (2.6%) increase in the NTI and DID, respectively, with a statistically significant uptick in trend noted after the second lockdown (β5) for ‘total antibiotics’ for NTI only (β5 = 1.6; 95% CI:0.17, 3.1). Quality assessment showed an increase in ‘Access’ antibiotics from 77% in March/2019 to 86% in March/2023; however, COVID-19 had no significant impact on WHO AWaRe classes. Conclusion COVID-19’s impact on antibiotic use quality and quantity appeared to be minimal, though an increase in utilization post-second lockdown coincided with healthcare system recovery. This suggests a nuanced impact of the pandemic, highlighting the importance of continued antimicrobial stewardship.

Early Antibiotic Exposure and Bronchopulmonary Dysplasia in Very Preterm Infants at Low Risk of Early-Onset Sepsis

The overutilization of antibiotics in very preterm infants (VPIs) at low risk of early-onset sepsis (EOS) is associated with increased mortality and morbidities. Nevertheless, the association of early antibiotic exposure with bronchopulmonary dysplasia (BPD) remains equivocal. To evaluate the association of varying durations and types of early antibiotic exposure with the incidence of BPD in VPIs at low risk of EOS. This national multicenter cohort study utilized data from the Chinese Neonatal Network (CHNN) which prospectively collected data from January 1, 2019, to December 31, 2021. VPIs less than 32 weeks' gestational age or with birth weight less than 1500 g at low risk of EOS, defined as those born via cesarean delivery, without labor or rupture of membranes, and no clinical evidence of chorioamnionitis, were included. Data analysis was conducted from October 2022 to December 2023. Early antibiotic exposure was defined as the total number of calendar days antibiotics were administered within the first week of life, which were further categorized as no exposure, 1 to 4 days of exposure, and 5 to 7 days of exposure. The primary outcome was the composite of moderate to severe BPD or mortality at 36 weeks' post menstrual age (PMA). Logistic regression was employed to assess factors associated with BPD or mortality using 2 different models. Of the 27 176 VPIs included in the CHNN during the study period (14 874 male [54.7%] and 12 302 female [45.3%]), 6510 (23.9%; 3373 male [51.8%] and 3137 female [48.2.%]) were categorized as low risk for EOS. Among them, 1324 (20.3%) had no antibiotic exposure, 1134 (17.4%) received 1 to 4 days of antibiotics treatment, and 4052 (62.2%) received 5 to 7 days of antibiotics treatment. Of the 5186 VPIs who received antibiotics, 4098 (79.0%) received broad-spectrum antibiotics, 888 (17.1%) received narrow-spectrum antibiotics, and 200 (3.9%) received antifungals or other antibiotics. Prolonged exposure (5-7 days) was associated with increased likelihood of moderate to severe BPD or death (adjusted odds ratio [aOR], 1.23; 95% CI, 1.01-1.50). The use of broad-spectrum antibiotics (1-7 days) was also associated with a higher risk of moderate to severe BPD or death (aOR, 1.27; 95% CI, 1.04-1.55). In this cohort study of VPIs at low risk for EOS, exposure to prolonged or broad-spectrum antibiotics was associated with increased risk of developing moderate to severe BPD or mortality. These findings suggest that VPIs exposed to prolonged or broad-spectrum antibiotics early in life should be monitored for adverse outcomes.

USE OF TAQMAN ARRAY TO INVESTIGATE INFECTION IN DIABETIC FOOT WOUNDS

IntroductionDiabetic foot disease is a major public health problem with an annual NHS expenditure in excess of £1 billion. Infection increases risk of major amputation fivefold. Due to the polymicrobial nature of diabetic foot infections, it is often difficult to isolate the correct organism with conventional culture techniques, to deliver appropriate narrow spectrum antibiotics. Rapid DNA-based technology using multi-channel arrays presents a quicker alternative and has previously been used effectively in intensive care and respiratory medicine.MethodsWe gained institutional and Local Ethics Committee approval for a prospective cohort study of patients with clinically infected diabetic foot wounds. They all had deep tissue samples taken in clinic processed with conventional culture and real-time PCR TaqMan array.Results50 samples were taken from 39 patients between October 2020 and March 2022. 84% of patient were male, 88% had type 2 diabetes. The ulcers were of variable chronicity prior to sampling (range 1–113 weeks) and mean HbA1c was 67.2mmol/mol. Ulcers were on the heel (3), midfoot (6) and forefoot (41). Minimum follow up was 3 months. 6 ulcers healed, 24 patients were admitted due to foot disease, there were 2 major amputations and 4 deaths. TaqMan array results were available a mean of 4.3 days earlier than culture results. 9 patients had negative conventional cultures and 8 were negative onarray testing. 17 patients had the same organisms detected on culture and array. 16 of these 17 had additional organisms detected by array. The most frequent organisms detected on array that were not detected by culture were Staphylococcus spp., Enterobacter, Pseudomonas and fungi.ConclusionTaqMan array shows promise in detecting infecting organisms from diabetic foot wounds and providing earlier results than standard culture, which may enable appropriate and timely antibiotic therapy.

Improving Antibiotic Prescribing for Children with Community-acquired Pneumonia in Outpatient Settings

To assess whether a two-phase intervention was associated with improvements in antibiotic prescribing among nonhospitalized children with community-acquired pneumonia. In a large health care organization, a first intervention phase was implemented in September 2020 directed at antibiotic choice and duration for children 2months through 17years of age with pneumonia. Activities included clinician education and implementation of a pneumonia-specific order set in the electronic health record. In October 2021, a second phase comprised additional education and order set revisions. A narrow spectrum antibiotic (eg, amoxicillin) was recommended in most circumstances. Electronic health record data were used to identify pneumonia cases and antibiotics ordered. Using interrupted time series analyses, antibiotic choice and duration after phase one (September 2020-September 2021) and after phase two (October 2021-October 2022) were compared with a preintervention prepandemic period (January 2016-early March 2020). Overall, 3570 cases of community-acquired pneumonia were identified: 3246 cases preintervention, 98 post-phase one, and 226 post-phase two. The proportion receiving narrow spectrum monotherapy increased from 40.6% preintervention to 68.4% post-phase one to 69.0% post-phase two (P<.001). For children with an initial narrow spectrum antibiotic, duration decreased from preintervention (mean duration 9.9days, SD 0.5days) to post-phase one (mean 8.2, SD 1.9) to post-phase two (mean 6.8, SD 2.3) periods (P<.001). A two-phase intervention with educational sessions combined with clinical decision support was associated with sustained improvements in antibiotic choice and duration among children with community-acquired pneumonia.

Shifting Patterns of Sputum Culture Testing and Antibiotic Usage Among Patients With Pneumonia Before and After the COVID-19 Pandemic

Abstract The coronavirus disease 2019 (COVID-19) pandemic has greatly shifted the attitude of the public and health care workers toward health care practices. Furthermore, this pandemic led to reduced diagnostic testing of various diseases worldwide. This study investigated the impact of the COVID-19 pandemic on health care practices, mainly focusing on sputum culture testing for pneumonia and how these changes affected antibiotic selection and health outcomes. We conducted a retrospective observational study at the Tokyo Medical University Ibaraki Medical Center between January 2018 and December 2021. We compared clinical outcomes during the pre–COVID-19 and post–COVID-19 periods. These outcomes included microbiological test implementation (eg, sputum culture test), length of hospital stay, and in-hospital mortality. Of the 698 patients, 384 (55.0%) were from the pre–COVID-19 period, and 314 (45.0%) were from the post–COVID-19 period. The post–COVID-19 period was associated with a lower ordering rate of sputum cultures (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.50–0.93). Furthermore, the post–COVID-19 period was associated with increased use of narrow-spectrum antibiotics (OR, 1.57; 95% CI, 1.12–2.21) and a higher rate of in-hospital death (OR, 1.78; 95% CI, 1.16–2.73). The COVID-19 pandemic has prompted changes in health care–seeking behaviors, affecting health care providers' diagnostic practices and potentially influencing patient outcomes. Our study outlines the importance of adapting health care strategies during pandemics. Further studies are required to understand the complex interplay among pandemic situations, diagnostic procedures, and patient prognosis.