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Special Issue on CDS Failures: A Rash Decision: Implementing an EHR-Integrated Penicillin Allergy Delabeling Protocol Without Adequate Clinician Support.
DOI: 10.1055/a-2595-4849
Authors: Plattner AS et al
Abstract
Approximately 10% of patients have a documented penicillin “allergy”; however, up to 95% have subsequent negative testing. These patients may receive suboptimal antibiotics, leading to longer hospitalizations and higher costs, rates of resistant and nosocomial infections, and all-cause mortality. To mitigate these risks in children, an inpatient penicillin allergy delabeling protocol was implemmented and integrated into the electronic health record (EHR) through a mixed methods approach of clinical decision support (CDS). The protocol implementation is described across three sequential phases: “Pilot”, “Active Antimicrobial Stewardship Program (ASP)”, and “Mixed CDS”. Several potential pitfalls were highlighted that may have contributed to poor clinician adoption. Patients were risk-stratified as non-allergic, low-risk, or high-risk based on history. Process measures included: evaluation rate, oral challenge rate for low-risk, and allergy referral rate for high-risk or low-risk when oral challenge was deferred. Primary outcome measure was penicillin allergy delabeling rate among low-risk or non-allergic. Balancing measures included rate of epinephrine or antihistamine administrations. The Pilot and ASP Phases used clinician education and an order set, but were mostly manual processes. The Mixed CDS Phase introduced interruptive alerts, dynamic text in note templates, and patient list columns to guide clinicians, but little education was provided. The Mixed CDS Phase had the lowest evaluation rate compared to the Pilot and Active ASP Phases (6.4% vs 25% vs 15%). However, when evaluation was performed, the Mixed CDS Phase had the highest oral challenge rate (33% vs 26% vs 13%) and delabeling rate (43% vs 33% vs 27%). No adverse events occurred. CDS tools improve clinician decision-making and optimize patient care. However, relying on CDS for complex clinical evaluations can lead to failure when clinicians cannot find the tool or appreciate the importance. Person-to-person communication can be vital in establishing a process and educating intended users for successful CDS implementat.
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Rapid and sensitive antimicrobial susceptibility testing of biofilm-forming bacteria using scalable paper-based organic transistors.
Authors: Rafiee Z et al
Abstract
A scalable, cost-effective paper-based organic field-effect transistor platform has been developed for rapid antimicrobial susceptibility testing (AST) of biofilm-forming pathogens. Traditional AST methods are costly, labor-intensive, and slow, with a lack of standardized biofilm models. This system directly tracks protons generated by biofilms, which serve as key indicators of bacterial metabolism under antibiotic exposure. A proton-sensitive PEDOT:PSS channel is employed, where metabolic proton activity de-dopes the transistor, reducing conductivity. The engineered paper substrate facilitates rapid, high-quality biofilm formation, improving assay reliability. The platform was validated on three clinically significant pathogens against frontline antibiotics, providing real-time, quantitative antibiotic efficacy profiles. Integrated with a microcontroller and machine learning algorithm, results are displayed on a liquid crystal display (LCD), classifying antibiotic concentration relative to the minimum inhibitory concentration with over 85% accuracy. This clinically translatable system offers a high-throughput, point-of-care solution for efficient infection management and antibiotic stewardship.
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Management practices and mortality predictors among Klebsiella pneumoniae infections across Lebanese hospitals: a multicenter retrospective study.
Authors: Itani R et al
Abstract
Background: Klebsiella pneumoniae is a significant cause of both community-acquired and nosocomial infections, leading to high morbidity and mortality rates. The increasing antimicrobial resistance among K. pneumoniae strains poses a critical challenge to effective treatment. This study aimed to assess the appropriateness of initial antimicrobial therapy, determine the 30-day all-cause mortality rate, and identify predictors of mortality among patients infected with K. pneumoniae in Lebanese hospitals.
Methods: A multicenter retrospective observational study was conducted across three university hospitals in Beirut, Lebanon. The study included hospitalized adult patients with confirmed K. pneumoniae infections. Kaplan-Meier survival analysis and log-rank tests were used to analyze time-to-mortality. Binary logistic regression was performed to identify predictors of mortality.
Results: Of 2,655 cases screened, 410 patients were enrolled, and 395 cases were included in the final analysis of the 30-day mortality after excluding those lost to follow-up. Nearly one-third of the isolates (36.8%) were extended-spectrum β-lactamase (ESBL)-producing, while 6.8% were carbapenem-resistant K. pneumoniae (CRKP). The most commonly prescribed empirical antibiotics were meropenem (31.7%), amikacin (28.5%), and ceftriaxone (22.2%). Around one-third of the patients (32.9%) received inappropriate initial antimicrobial therapy. The 30-day mortality rate was 14.4%. Main predictors significantly associated with mortality in patients with K. pneumoniae infection were solid cancer (adjusted odds ratio [AOR] = 7.82, P < 0.01), coronary artery disease (AOR = 4.81, P = 0.01), age ≥ 65 years (AOR = 4.22, P = 0.02), type II diabetes mellitus (AOR = 3.96, P = 0.01), receiving inappropriate initial antimicrobial therapy (AOR = 2.96, P = 0.02), infection with CRKP isolates (AOR = 2.53, P = 0.03), and having a higher Charlson comorbidity index (AOR = 1.61, P = 0.001).
Conclusions: The study highlights the critical need for effective antimicrobial stewardship and tailored infection control protocols to mitigate the high resistance rates and improve patient outcomes in Lebanon. Emphasis should be placed on enhancing the monitoring of local resistance patterns and using these data to guide the selection of appropriate empirical therapy to reduce mortality associated with K. pneumoniae infections.
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A study on the effectiveness of an antifungal stewardship program in immunocompromised patients in a tertiary-care teaching hospital: The Antifungal Stewardship (TAFS) Study.
Authors: Jacob A et al
Abstract
Introduction: Anti-fungal stewardship (AFS) is a neglected aspect of antimicrobial stewardship programs. This study aimed to examine the effectiveness of an AFS program to ensure rational prescribing of antifungals via a post-prescription review and feedback method.
Methods: In this prospective, interrupted time series analysis, AFS was done on adult patients admitted to the department of hematology in a tertiary care hospital in South India. In the pre-intervention phase, patients on anti-fungal therapy for more than 48 hours were identified and baseline data was collected. In the intervention phase, patients on antifungals for >48 hours were assessed by an AFS team including an infectious diseases specialist and appropriate recommendations were made regarding modification or discontinuation of the antifungals where required. Acceptance of the intervention by the treating team and clinical outcomes were recorded
Results: A total of 193 courses of antifungal therapy in 152 patients were analyzed over 6 months, of which 107 courses belonged to the pre-intervention phase and 86 were in the intervention phase. In the intervention phase, the AFS teams recommended that 15 (17.44%) of antifungal prescriptions be modified. Among these, 66% of the recommendations were accepted by the treating physician. Days of therapy per 1000 patient days were calculated for each individual anti-fungal drug and there was a significant reduction in consumption of antifungals, particularly voriconazole, posaconazole and echinocandins in the intervention phase. There was no statistically significant difference in the in-hospital mortality [26.16% vs 23. 25% (p = 0.64)] between the two groups
Conclusion: In this study, a focused post prescription review and feedback in an antifungal stewardship program appeared to significantly decrease the prescription of antifungal medication without adversely affecting patient outcomes.
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Demystifying Prolonged Antibiotic Use for Blood Culture-negative Sepsis Evaluations in the Neonatal Intensive Care Unit.
Authors: Sivakumar N et al
Abstract
Objective: This study aimed to determine the incidence and clinical characteristics of infants evaluated and treated with a prolonged course of antibiotics for culture-negative sepsis in a quaternary Neonatal Intensive Care Unit (NICU) over a 4-year period.
Study design: Retrospective chart review of patients in the NICU at Children’s Hospital of Philadelphia who had negative blood cultures and received ≥5 days of antibiotics. Data collection included demographics, clinical and laboratory data, and underlying diagnoses. Statistical analysis included Mann-Whitney and chi-square tests, and multivariable logistic regression.
Results: 774 culture-negative sepsis evaluations were identified where antibiotic treatment was continued ≥5 days. While the majority were attributed to a focal etiology, 146 had negative blood cultures and no focal source. Infants with no focal source were younger at the time of sepsis evaluation, of greater gestational age, and more frequently required extracorporeal membrane oxygenation (P < 0.001). In multivariable analysis, evaluations for early-onset disease and need for extracorporeal membrane oxygenation were increased among infants with no focal source (P < 0.01). Although rates of invasive ventilation, and central venous catheters were similar, length of stay and mortality were significantly higher in late-onset episodes (P < 0.001 and P = 0.029, respectively). Consultation with the infectious disease team increased during the study period (P = 0.002).
Conclusions: Although it is challenging to limit the initiation of antibiotics in infants with complex underlying disease processes with concern for sepsis, minimizing antibiotic use can be achieved by timely discontinuation when cultures are negative. A robust antimicrobial stewardship program can identify valid reasons for prolonged antibiotic administration and suggest approaches to minimize antibiotic exposure.
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Assessment of in vitro antimicrobial activities of ceftolozane/tazobactam and ceftazidime/avibactam against carbapenem-resistant Pseudomonas aeruginosa clinical isolates.
Authors: Salem D et al
Abstract
Background: Carbapenem resistant Pseudomonas aeruginosa (P. aeruginosa) is a global health concern that poses a challenge to treat in health care facilities. Ceftazidim/avibactam and ceftolozane/tazobactam have a potential role in treatment of multi-drug resistant phenotypes including carbapenem resistant P. aeruginosa. Therefore, the aim was to assess the in vitro antimicrobial activity of ceftazidime/avibactam and ceftolozane/tazobactam against carbapenem-resistant P. aeruginosa (CRPA) strains with different β-lactamase/carbapenemase genes.
Methods: Sixty CRPA isolates identified from clinical samples were examined for antimicrobial susceptibility including ceftazidim/avibactam and ceftolozane/tazobactam by Vitek2 compact system, and carbapenemase production by modified carbapenem inactivation method (mCIM) test and carbapenemase producing genes by polymerase chain reaction (PCR).
Results: Isolates were resistant to imipenem in 96.7% and meropenem in 88.3%. of isolates. Carbapenemase production by mCIM test was 70% compared to 73.3% by (PCR). Carbapenemase encoding genes blaNDM, blaVIM and blaOXA-48 were detected in 60%, 41.7% and 25% respectively while blaIMP and blaKPC weren’t identified in this study. Among CRPA, both ceftazidim/avibactam and ceftolozane/tazobactam; were sensitive in only 11.7% of the isolates. Resistance to ceftazidim/avibactam and ceftolozane/tazobactam in isolates owning blaNDM, blaVIM, blaOXA-48 and those having combined blaNDM, blaVIM and blaOXA-48 carbapenemase resistance genes were 97.2%, 92%, 100% and 100% respectively.
Conclusion: Modified carbapenem inactivation method test gave satisfactory results and could be used as an alternative to expensive genotypic methods. Ceftazidim/avibactam and ceftolozane/tazobactam were unsuccessful against carbapenem resistant P. aeruginosa isolates carrying carbapenemase genes especially metallo-β lactamase genes. Therefore, it is essential to detect susceptibility patterns to newly introduced β-Lactam/β-Lactamase inhibitor combinations due to the emerging resistance to these therapeutics.
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Antimicrobial resistance and vaccines in Enterobacteriaceae including extraintestinal pathogenic Escherichia coli and Klebsiella pneumoniae.
Authors: Cabrera A et al
Abstract
Antimicrobial-resistant Enterobacteriaceae are increasingly a clinical challenge. In particular, extraintestinal pathogenic Escherichia coli and Klebsiella pneumoniae threaten public health. Vaccination presents a long-term strategy to reduce both drug-susceptible and resistant infections while maintaining current clinical therapies. The review aims to emphasize the need for vaccines targeting extraintestinal pathogenic E. coli and K. pneumoniae by providing an overview of disease burden, antimicrobial resistance, therapeutics, and vaccine development.
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In-vitro antimicrobial activity of new antimicrobial agents against Streptococcus pneumoniae and potential resistance mechanisms: a multicenter study.
Authors: Lei Z et al
Abstract
Background: Streptococcus pneumoniae is a major cause of invasive and non-invasive diseases, particularly in children and immunocompromised individuals, with an annual mortality of approximately 800,000 children worldwide. The rise of antibiotic-resistant strains complicates treatment, especially with increasing resistance to penicillin, macrolides, and fluoroquinolones. The study on the resistance of newly developed antimicrobial agents against S. pneumoniae was rarely reported. Furthermore, understanding the relationship between serotypes, resistance mechanisms, and virulence in S. pneumoniae is essential for disease management and vaccine development.
Methods: A total of 208 S. pneumoniae isolates were collected across nine hospitals in seven Chinese cities/provinces from January 2023 to June 2024. Molecular characteristics were analyzed using whole-genome sequencing to identify serotypes, sequence types, virulence genes, and potential resistance mechanisms. Antibiotic susceptibility test (AST) was performed against 14 agents, involving new antibiotics (eravacycline, omadacycline, nemonoxacin, and contezolid).
Results: Serotypes 19 F (24.6%) and 23 F (11.1%) predominated, with vaccine coverage rates of PCV13 at 66.8%. High resistance rates in S. pneumoniae were observed for erythromycin (208/208, 100%), clindamycin (197/208, 94.7%), and tetracycline (192/208, 92.3%). 13.5% (28/208) and 2.9% (6/208) strains were intermediate and resistant to penicillin, respectively. The new antibiotics showed low resistance, namely, 1.9% (4/208), 0.5% (1/208), 1.9% (4/208), and 7.2% (15/208) resistant to eravacycline, omadacycline, contezolid, and nemonoxacin, respectively. Resistance mechanisms included mutations in 23S rRNA for oxazolidinones, tet genes for tetracyclines, and gyrA/parC for fluoroquinolones.
Conclusions: S. pneumoniae in China exhibits high genetic diversity and significant antibiotic resistance, underscoring the need for continuous surveillance and updated vaccines. New antibiotics remain effective against multidrug-resistant strains, offering potential treatment options in clinical settings.
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Development and Validation of a Cephalosporin Allergy Clinical Decision Rule
Authors: Cox, F et al.
Abstract
Background: Like penicillin allergy labels, cephalosporin allergy labels go largely unverified and drive inappropriate antibiotic use. Clinical decision rules (CDR) have been validated to identify low-risk penicillin allergy labeled patients suitable for direct oral challenge (DOC); however, the generalizability to cephalosporin allergy remains uncertain.
Methods: Cephalosporin allergy tested cohorts from three hospitals in Australia were used for validation of a cephalosporin allergy CDR, based on clinical variables utilised in the published penicillin allergy decision rule (PEN-FAST). Patients with a cephalosporin allergy label underwent allergy testing. North American tested cohorts were used for external validation.
Findings: From an Australian validation cohort of 228 patients and an external cohort of 167 patients, the four clinical features associated with a positive penicillin allergy from PEN-FAST showed similar associations to a positive cephalosporin test, with minor adjustments to scoring. Validation showed an AUROC of 0·921. A cut-off of less than three points for the newly directed CEPH-FAST was chosen to classify a low risk of cephalosporin allergy, for which six of 105 patients (5·7%) had positive allergy testing results.
Interpretation:Utilising the previously published and internationally validated tool PEN-FAST, we validated the same criteria with minor modifications for low-risk cephalosporin allergies. The results suggest that a CEPH-FAST score of less than three is associated with a high negative predictive value and could be used by clinicians and antimicrobial stewardship programs to identify patients with low-risk cephalosporin allergies at the point of care, following local validation, who could proceed to DOC or use non-cross-reactive cephalosporins.
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Dynamic global variation in resistance and hypervirulence of carbapenem-resistant Klebsiella pneumoniae between 2010 and 2023
Authors: Zhang Feilong
Abstract
• 26,713 qualified CRKP genomes with spatiotemporal metadata from 90 countries (2010-2023) were selected for genomic analysis.
• Genomic characteristics of global CRKP presented divergent trend in resistance and hypervirulence between before and during the COVID-19 pandemic.
• Substantial interregional molecular heterogeneity existed.
• Isolation of non-clinical CRKP underscored the importance for One Health-driven surveillance.
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Causal Relationship Between Helicobacter Pylori Antibodies And Immune Thrombocytopenia: A Mendelian Randomization Study
Authors: Yuzhan Chen
Abstract
Background: Previous observational studies have suggested a potential causal relationship between Helicobacter pylori (H. pylori) infection and Immune thrombocytopenia (ITP). However, the evidence for causal inference remains contentious, and the underlying mechanisms require further investigation. In order to delve deeper into the relationship between H. pylori and ITP, we conducted a Mendelian randomization (MR) analysis.
Method: In this study, we used two-sample Mendelian Randomization (MR) to assess the causality of seven different specific protein antibodies targeting H. pylori on ITP. 76 single nucleotide polymorphisms (SNPs) related to H. pylori antibodies levels were obtained from the European Bioinformatics Institute (EBI). Summary data of ITP was obtained from the FinnGen database, Inverse variance weighted (IVW) analysis was identified as our main method. To ensure the reliability of the findings, many sensitivity analyses were performed.
Result: Genetically predicted serum levels of H. pylori GroEL antibodies were positively associated with an increased risk of ITP (odds ratio [OR] = 1.802, 95% CI 1.106–2.936, P = 0.01799). No causal relationship was found between other H. pylori antibodies and ITP.
Conclusion: The outcomes derived from our two-sample Mendelian randomization analysis demonstrate a discernible link between the levels of H. pylori GroEL antibodies and an augmented susceptibility to ITP. However, it is imperative to expand the sample size further in order to corroborate the correlation between H. pylori infection and ITP.
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Demystifying Prolonged Antibiotic Use for Blood Culture-negative Sepsis Evaluations in the Neonatal Intensive Care Unit
Authors: Sivakumar
Abstract
Objective: This study aimed to determine the incidence and clinical characteristics of infants evaluated and treated with a prolonged course of antibiotics for culture-negative sepsis in a quaternary Neonatal Intensive Care Unit (NICU) over a 4-year period.
Study design: Retrospective chart review of patients in the NICU at Children’s Hospital of Philadelphia who had negative blood cultures and received ≥5 days of antibiotics. Data collection included demographics, clinical and laboratory data, and underlying diagnoses. Statistical analysis included Mann-Whitney and chi-square tests, and multivariable logistic regression.
Results: We identified 774 culture-negative sepsis evaluations where antibiotic treatment was continued ≥5 days. While the majority were attributed to a focal etiology, 146 had negative blood cultures and no focal source. Infants with no focal source were younger at the time of sepsis evaluation, of greater gestational age, and more frequently required extracorporeal membrane oxygenation (P < 0.001). In multivariable analysis, evaluations for early-onset disease and need for extracorporeal membrane oxygenation were increased among infants with no focal source (P < 0.01). Although rates of invasive ventilation, and central venous catheters were similar, length of stay and mortality were significantly higher in late-onset episodes (P < 0.001 and P = 0.029, respectively). Consultation with the infectious disease team increased during the study period (P = 0.002).
Conclusions: Although it is challenging to limit the initiation of antibiotics in infants with complex underlying disease processes with concern for sepsis, minimizing antibiotic use can be achieved by timely discontinuation when cultures are negative. A robust antimicrobial stewardship program can identify valid reasons for prolonged antibiotic administration and suggest approaches to minimize antibiotic exposure.