Optimal Antibiotic Research Articles

Determining the optimal antibiotic duration for skin and soft tissue infections.

Optimal duration of therapy in SSTIs - a heterogeneous group of infections - remains unknown. The advances in knowledge of antibiotic duration of treatment in selected SSTIs that can impact clinical practice and published in the last 18 months are reviewed. Recent evidence indicates that few patients receive guideline concordant empiric antibiotics and appropriate duration in the United States, although this likely can be extrapolated to other countries. One of the most commonly identified opportunities to improve antibiotic stewardship is duration of therapy more than 10 days. The long-standing debate regarding the significance of abscess size and its impact on clinical response to antibiotics, following proper drainage, is increasingly shifting towards the conclusion that abscess size is not directly associated with cure.In obese patients with SSTI, there is no benefit to longer antibiotic durations for SSTIs in patients with obesity, and it appears that longer antibiotic duration of therapy was associated with increased treatment failure. In diabetic foot infections (DFO), two randomized studies suggest that in the presence of osteomyelitis, the total duration of antibiotic therapy for patients treated nonsurgically does not need to be more than 6 weeks. In a prospective, randomized, noninferiority, pilot trial, patients with DFO who underwent surgical debridement and received either a 3-week or 6-week course of antibiotic therapy had similar outcomes and antibiotic-related adverse events. In patients with necrotizing soft tissue infections, successive observational studies clearly suggest that short duration of antibiotic treatment after NSTI source control is as well tolerated and effective as a longer course. It appears that 48 h would be enough. The possibility of fixed versus individualized approaches to therapy for common bacterial infections, including SSTIs merits to be considered seriously. Fully individualized therapy may be an ideal approach to maximize the benefits and minimize the harms of antimicrobials. Much more work is needed before this strategy becomes feasible. There is increasing evidence that shorter duration of treatment is better in different types of SSTIs. Paradoxically, evaluation of real-life clinical practice indicates that long treatments continue to be commonly given to this population.

P-1136. Enhancing Pediatric Care: Antimicrobial Stewardship Through 24/7 Pharmacist-Driven Rapid Diagnostics for Gram-Negative Bacteremia

Abstract Background Rapid diagnostic testing (RDT) in adult bacteremic patients (pts) provides quick organism identification, including resistance genes and can improve time to optimal antibiotic therapy (OAT). Pharmacist-driven RDT (Rx-RDT) interventions [24 hours/day and 7 days/week (24/7)] for pediatric gram-negative bacteremia GNB is limited. Objective was to evaluate outcomes before and after implementation a 24/7 Rx-RDT interventions (INT) for treatment of pediatric GNB. Methods Retrospective cohort study analyzed pediatric pts (age < 18 years) with GNB secondary to Escherichia coli, Klebsiella pneumoniae or Klebsiella oxytoca admitted to the Children’s Hospital comparing outcomes before and after implementation of 24/7 Rx-RDT INT. Pre-RDT group included pts admitted from 1/1/14-12/31/14; Pre-RDT 24/7 group embodied weekday antimicrobial stewardship (AMS) duties from 1/1/19-7/5/21; and Post-RDT 24/7 from 7/6/21-8/31/22. Polymicrobial bacteremia or concomitant fungemia were excluded. Results A total of 132 pts were included in 3 groups: Pre-RDT (n=35); Pre-RDT 24/7 (n=55); Post-RDT 24/7 (n=42). Baseline demographics were mainly similar with Hispanic predominance (Table 1). In Pre-RDT, Pre-RDT 24/7, and Post-RDT 24/7, respectively, E. coli was most common (65.7% vs 60% vs 54.8%; p=0.666) with CTX-M gene detection (associated with the extended spectrum beta-lactamase (ESBL) phenotype) in latter 2 groups (9.1% vs 26.1%; p=0.013) followed by K. pneumoniae (28.6% vs 25.5% vs 33.3%; p=0.666) with ESBL 21.4% in latter groups; p >0.05). Pts were on OAT at the time of gram-stain (GS) results in 85.7% vs 74.5% vs 59.5%; p=0.034. For pts who were not on OAT at GS results, time to OAT from blood culture collection was lowest in the Post-RDT 24/7 group (85.6 vs 26.2 vs 15.7 hours; p=0.156); time to OAT was faster from time of RDT results Post-24/7 RDT (7.9 vs 2.4 hours; p=0.028). Length of stay (19.5 vs 12.9 vs 13.3 days; p=0.601) and 30-day mortality were similar (11.4% vs 14.5% vs 9.5%; p=0.746); 30-day mortality occurred with Hispanics in all groups (18.2% vs 16.7% vs 14.4%). Night/Weekend pharmacists performed 44% of the Post-RDT 24/7 INT. Conclusion Implementation of Rx-RDT interventions 24/7 reduced time to OAT by 30% for pediatric GNB. Night/Weekend pharmacists were integral to our AMS program. Disclosures All Authors: No reported disclosures

172. Impact of 24/7 Rapid Diagnostic Testing Pharmacist Interventions and Infectious Diseases Consultation in Pediatric Staphylococcus aureus Bacteremia

Abstract Background The benefits of pharmacist interventions using rapid diagnostic testing (RDT) and Infectious Diseases (ID) consultation for Staphylococcus aureus bacteremia (SAB) have been documented in adults, but data on pediatric patients is sparse. The study objectives were to evaluate the impact of 24/7 pharmacist-led RDT interventions and pediatric ID consultation on clinical outcomes in pediatric SAB. Methods This retrospective cohort study analyzed pediatric patients (age < 18 years) with SAB admitted to Children’s Hospital comparing outcomes before and after implementation of 24/7 pharmacist-led RDT interventions. Pre-intervention (Pre-RDT) group included patients admitted from February 2013 to January 2015 and the post-intervention (Post-RDT) group from August 2021 to July 2023. Premature infants (< 36 weeks gestational age) and patients with polymicrobial bacteremia or fungemia were excluded. Results A total of 101 patients were included: Pre-RDT (n=51) and Post-RDT (n=50). Most patients were male (68.3%) and white (61.4%) with similar baseline characteristics (Table 1). The median time to optimal antibiotic (TOAT) from blood culture collection was lower in the Post-RDT group than the Pre-RDT group (23.9 vs 29.0 hours; p=0.673) for MRSA and MSSA isolates. The Post-RDT group had lower median TOAT for MSSA (24.8 vs 87.7 hours; p < 0.001) with higher use of beta-lactams (Figure 1), lower hospital length of stay (LOS) (12 vs 17 days; p=0.007), lower ICU admissions (40.0% vs 64.7%; p=0.017), and shorter ICU LOS (14 vs 17 days; p=0.022) than patients in the Pre-RDT group. Post-RDT patients had fewer 30-day readmission (22.0% vs 23.5%; p > 0.05) and in-hospital mortality (4% vs. 7.8%; p > 0.05) than Pre-RDT patients. ID was consulted more frequently in the Post-RDT group (94.0% vs. 56.9%; p < 0.001). In-hospital mortality was lower with ID consultation than without it (2.6% vs. 16.0%; p=0.032). Conclusion Integration of 24/7 RDT pharmacist interventions and pediatric ID consultations were associated with improved clinical outcomes (TOAT for MSSA, hospital and ICU LOS and in-hospital mortality) in pediatric patients with SAB, highlighting the effectiveness of these interventions in a pediatric antimicrobial stewardship framework. Disclosures All Authors: No reported disclosures

301. Clinical impact of a Streptococcus pneumoniae PCR assay on pleural fluid specimens for children with complicated pneumonia

Abstract Background While Streptococcus pneumoniae (Spn) is the predominant pathogen in pediatric complicated community acquired pneumonia (cCAP), it is infrequently recovered by culture-based methods. Without Spn or another pathogen detected, patients often remain on inappropriately broad-spectrum therapy. We studied the real-world clinical impact of a newly implemented, lab developed Spn PCR assay, with target genes lytA, piaB, SP2020, for pleural fluid specimens. Methods We compared pathogen detection, antibiotic usage, and outcomes in children hospitalized with cCAP requiring pleural effusion or empyema drainage at Children’s Hospital Colorado between 2016 – 2023. The study population was divided into two diagnostic periods: pre-Spn PCR (October 1, 2016 – July 26, 2022) and post-Spn PCR (July 27, 2022 – September 30, 2023). Kaplan Meier curves and log-rank tests compared time from hospital admission to pathogen detection, optimal therapy, and MRSA therapy discontinuation between periods. Optimal therapy was pre-defined as pathogen-directed therapy or per institutional guidelines (ampicillin in most cases with no pathogen). Results Patient characteristics and illness severities were similar across the pre-Spn PCR (N=149) and post-Spn PCR (N=79) periods, and pleural fluid drainage occurred most frequently on hospital day 2 (Table 1). The post-Spn PCR cohort had a higher percentage with any pathogen detected (72.4% vs. 38.5%, p < 0.001), driven by more Spn detections (45.6% vs. 14.1%, p < 0.001) (Table 2). Time to pathogen detection was shorter in the post-Spn PCR period (p < 0.001, Figure 1). Post-Spn PCR patients were more likely to reach optimal antibiotic therapy (84.8% vs. 51.4%, p < 0.001), with shorter median time to optimal therapy (5.0 days vs. 10.3 days, p < 0.001, Figure 2A) and shorter median time to MRSA antibiotic discontinuation (1.5 days vs. 2.5 days, p = 0.03, Figure 2B). There were no differences in hospital length of stay or readmissions (Table 2). Conclusion Molecular detection of Spn in pleural fluid of children with cCAP resulted in a significant increase in causative pathogen identification, optimization of antibiotics, and decreased exposure to MRSA antibiotics, demonstrating that PCR is a clinically impactful addition to conventional pneumonia diagnostics. Disclosures Molly Butler, PhD, Pfizer: Conference Attendance Sarah A. Jung, PhD, Cobio Diagnostics: Advisor/Consultant|Karius Inc: Advisor/Consultant|Roche Diagnostics: Advisor/Consultant Edwin J. Asturias, MD, BioFire: Grant/Research Support|Hillevax: Advisor/Consultant|Merck: Advisor/Consultant|Moderna: Advisor/Consultant|Pfizer: Grant/Research Support Samuel R. Dominguez, MD, PhD, BIofire Diagnostics: Advisor/Consultant|BIofire Diagnostics: Grant/Research Support|DelveBio: Grant/Research Support|Karius: Advisor/Consultant|Karius: Grant/Research Support|Pfizer: Grant/Research Support

177. AMR-Informed Antibiotic Use Metrics

Abstract Background Antimicrobial resistance (AMR) poses a significant public health threat, and efforts are underway to monitor and reduce unnecessary antibiotic usage. The Standardized Antibiotic Administration Ratio (SAAR) measures unit and hospital consumption of antibiotics by adjusting for facility characteristics. However, SAAR currently does not consider the prevalence rates of AMR that could justify or challenge antibiotic usage. Our objective is to develop an optimization function that identifies the best antibiotic choice for sepsis caused by Gram-negative bacilli (GNB). Optimization functions determine the optimal solution given specific constraints. Methods This observational cohort study included all adult patients meeting the CDC sepsis criteria and admitted to any of the 10 BJC acute care hospitals between 2016 and 2021. We focused on GNB isolated from clinical cultures, specifically the 17 most common species. We selected 15 commonly used antibiotics with activity against GNB (Table 1). Initially, we calculated the antibiotic weights to determine the relative coverage of each antibiotic, expressed as the ratio of GNB susceptible to all cultured GNB. The optimization function then constrained the optimal choice to the antibiotic with the lowest weight that still exhibited activity against the ultimately isolated strain. The resulting optimal antibiotic weights were averaged per hospital and study year and reported as a ratio to the weights of antibiotics used, akin to SAAR. Results Our study included 11,515 GNB cultures obtained from 9,531 patients. GNB were isolated from urine (40.5%), blood (20.5%), and respiratory specimens (20.3%). We present the antibiotic weights in Table 1, along with the representative ratios of empiric and directed observed-to-optimal antibiotic weights across BJC hospitals during the study period (Figs 1 and 2). Additionally, we contrast the SAAR trends for the same hospitals in Fig. 3. Conclusion Our optimization function selects the narrowest spectrum antibiotic and facilitates comparisons in antibiotic spectrum usage while considering existing AMR dynamics. It provides actionable insights and complements SAAR's metric of antibiotic duration. Disclosures M Cristina Vazquez Guillamet, MD, BNGO: Stocks/Bonds (Public Company)|Carisma Therapeutics: Stocks/Bonds (Public Company)|Ocugen: Stocks/Bonds (Public Company)

The Impact of Antibiotics on Latency When Given at the Time of Membrane Rupture Prior to Viability.

It is well established that antibiotics administered in preterm prelabor rupture of membranes increases latency to delivery. While data is limited for membrane rupture prior to viability, antibiotics may also increase latency in this population. To assesses the effect of prophylactic antibiotics on the duration of latency in individuals with previable prelabor rupture of membranes. Retrospective cohort of pregnancies with previable prelabor rupture of membranes prior to 23 weeks, 0 days in a single health system(2013-2022). Patients opting for termination or with a contraindication to expectant management were excluded. The primary outcome was latency from previable prelabor rupture of membranes diagnosis to delivery. Secondary outcomes included subanalysis by gestational age as well as maternal and neonatal morbidity and mortality. Bivariate statistics compared patients who did and did not received antibiotics. Kaplan-Meier/Cox proportional hazards ratios using significant covariates(p<0.1) in bivariate analysis models examined antibiotic impact on latency. Of 115 patients, 46(40%) met inclusion criteria, of whom 34(74%) received latency antibiotics. Median latency did not differ with antibiotic receipt(1 week, [0.4,2.6] versus 0.6 weeks [0.3,0.9], p=0.27). When adjusted for gestational age at rupture of membranes, antibiotics were not associated with longer latency(hazard ratio1.33 [0.91,1.93]). Antibiotic receipt was associated with lower rates of previable delivery(23.0 weeks, [22.7, 24.0] versus 21.3 weeks [20.5,23.1], p=0.006). Adjusted odds of previable delivery remained lower with receipt of antibiotics(adjusted odds ratio 0.20, [0.04,0.90]). Antibiotics were associated with longer latency in patients with rupture of membranes at less than 22 week's gestation(2.4wks [1.3,4.4] vs 0.6wks [0.1,0.9], p=0.02). Antibiotic administration at the time of previable prelabor rupture of membranes was associated with longer latency if prior to 22 weeks' gestation. Antibiotic administration increased the odds of delivering after viability. Further study should address optimal antibiotics strategies for this unique population.

Incidence of surgical infection in cefazolin 3 g versus 2 g for colorectal surgery in obese patients.

To compare the incidence of surgical site infection (SSI) between cefazolin 3 g and 2 g surgical prophylaxis in patients weighing ≥120 kg that undergo elective colorectal surgery. A multicenter, retrospective cohort study was performed utilizing a validated database of elective colorectal surgeries in Michigan acute care hospitals. Adults weighing ≥120 kg who received cefazolin and metronidazole for surgical prophylaxis between 7/2012 and 6/2021 were included. The primary outcome was SSI, which was defined as an infection diagnosed within 30 days following the principal operative procedure. Multivariable logistic regression was used to identify variables associated with SSI; the exposure of interest was cefazolin 3 g surgical prophylaxis. A total of 581 patients were included; of these, 367 (63.1%) received cefazolin 3 g, while 214 (36.8%) received 2 g. Patients who received cefazolin 3 g had less optimal antibiotic timing (324 [88.3%] vs 200 [93.5%]; P = .043) and a higher receipt of at least 1 of the prophylaxis antibiotics after incision (22 [6%] vs 5 [2.3%]; P = .043). There was no SSI difference between cefazolin 3 g and 2 g cohorts (23 [6.3%] vs 16 [7.5%], P = .574). When accounting for age, smoking status, and surgical duration, cefazolin 3 g was not associated with a reduction in SSI (adjOR, .64; 95%CI, .32-1.29). Surgical prophylaxis with cefazolin 3 g, in combination with metronidazole, was not associated with decreased SSI compared to 2 g dosing in obese patients undergoing elective colorectal surgery.

Varicella cellulitis in children (personal experience)

Annotation. The frequency of complications with varicella is 5-30%, and their level is much higher in patients with immunodeficiencies. In 8-50% of hospitalized children with varicella virus infection develop skin and soft tissue complications such as cellulitis, lymphadenitis, abscess, hysteria, toxicoderma. They are located on vulnerable parts of the body against the background of a state of anergy in a sick child, which is caused by the varicella virus. The aim is highlight clinical and diagnostic features and methods of treatment of varicella virus cellulitis in children based on own experience and according to literature sources. The high frequency of complications is associated with untimely detection of signs of inflammation and untimely treatment in case of secondary flora joining. The main etiological factors of superinfection are β-hemolytic streptococcus group A and staphylococcus aureus. Recently, cellulitis of the subcutaneous tissue is one of the most serious complications in patients with varicella virus infection. The clinical picture of this complication includes local and general manifestations. Local symptoms are accompanied by pronounced redness in the affected area, a significant increase in tissue volume due to swelling, intense, throbbing pain that worsens with touch or movement, the presence of purulent secretions from the affected area, compaction or softening of tissues at the site of the lesion, local hyperthermia. Treatment of varicella cellulitis involves a wide range of measures, which include: antibiotic therapy, drainage of purulent foci, symptomatic treatment, local treatment, supportive therapy, physiotherapy, observation and control. Before determining the optimal antibiotic, it is important to take into account the regional characteristics of the resistance of microorganisms and information about the typical causative agents of varicella cellulitis. Broad-spectrum antibiotics such as amoxicillin with clavulanic acid, ceftriaxone, clindamycin, or vancomycin are usually used for treatment. So, the main etiological factors causing complications in the form of necrotic cellulitis on the background of varicella virus are β-hemolytic streptococcus group A and Staphylococcus aureus. Diagnosis of varicella cellulitis includes a set of examination methods to confirm the diagnosis: daily examination of the child's body surface for inflammatory foci. The optimal treatment tactic is combined therapy (surgical and conservative treatment). Vaccination is recommended for children who are in risk groups – patients with oncology who receive cytostatics, corticosteroids; children with congenital and acquired immunodeficiencies.

Elective Treatment Strategy for Knee Prosthetic Joint Infection.

Prosthetic joint infection (PJI) is a complication, rarely encountered in daily clinical practice, but its treatment is frequently unsuccessful. In this report, we describe the treatment strategy used at our hospital, which has provided stable therapeutic results. We conducted a retrospective analysis of infections following knee arthroplasty at our hospital between April 2005 and December 2022. Post-total knee arthroplasty (TKA) infection occurred in 26 of 2132 patients (1.2%), and post-unicompartmental knee arthroplasty (UKA) infection occurred in six of 842 patients (0.7%); the difference was not significant (p=0.22). Infection occurred ≤3 months postoperatively in 13 patients with TKA and three with UKA, and ≥4 months postoperatively in 13 patients with TKA and three with UKA. Recurrent infection was observed in five patients with TKA and no patients with UKA. We did not conduct surgery for patients with PJI until causative bacteria were identified. We performed debridement, antibiotics, and implant retention (DAIR), with debridement of the synovium and insert replacement. Irrigation or drain placement was not conducted. The appropriate antibiotic was administered at a sufficient dose for a sufficiently long period, and the transfer of antibiotics into the bone marrow was not considered. Although some cases of recurrence were noted, treatment was successful in all cases, with no instances of obvious implant loosening or medullary lesions. In the absence of implant loosening, the post-arthroplasty infection can be controlled by elective debridement surgery and selective administration of the optimal antibiotic.

A study for the genotoxicity assessment of substances containing probiotic candidates in the in vitro TK6 cell micronucleus test: Influence of low pH conditions and antibiotic supplementation on the test results

BackgroundWhen assessing the genotoxicity of substances containing probiotic candidates, such as lactic acid-producing bacteria, using the in vitro micronucleus test (MNT), bacterial growth in the test medium may reduce the pH of the medium. The low medium pH is known to induce cytotoxicity and false-positive results. In the TK6 cell system, it is difficult to completely remove the bacteria from the medium by washing post-treatment, leading to bacterial growth during the recovery period in the short-term treatment. In the present study, the low pH range yielding false positives in the TK6 cell MNT was investigated using media supplemented with acetic, lactic, or formic acids, which are non-genotoxic bacterial metabolites. Additionally, to suppress the bacterial growth during the recovery period using antibiotics, i.e., penicillin/streptomycin (P/S), gentamicin sulfate (GM), and amphotericin B (AP), the maximum applicable concentrations of them that did not affect TK6 cell growth or micronucleus induction were determined. Then, we conducted an MNT using a substance containing live lactic acid-producing bacteria to verify the effectiveness of the antibiotics.ResultsAcetic, lactic, and formic acids induced micronuclei in TK6 cells (false positive) at an initial pH of ≤ 6.2 and ≤ 6.0 in 3 h treatment with and without S9 mix, respectively, and of ≤ 6.7 in the continuous treatment. Media supplemented with P/S, GM, and AP did not affect TK6 cell growth or micronucleated cell frequencies in the negative and positive controls ≤ 400 unit/mL-400 µg/mL, ≤ 250, and ≤ 20 µg/mL, respectively. In an MNT with fermented milk containing live lactic acid-producing bacteria, supplementation with P/S or GM to media for the recovery cultures suppressed the bacterial growth, decreasing pH, and cytotoxicity.ConclusionThis study revealed the low pH ranges yielding false positives in the TK6 cell MNT under short-term and continuous treatment conditions. These values will serve as references for interpreting the biological relevance of results. Under short-term treatment, optimal antibiotic supplementation in recovery cultures suppressed bacterial growth in the test substance and prevented the decrease in pH that could yield false positives. This approach might be useful for evaluating the genotoxicity of test substances containing probiotic candidates using the MNT.

Clinical Impact of Pleural Fluid Streptococcus pneumoniae Polymerase Chain Reaction Testing in Children With Complicated Pneumonia.

While Streptococcus pneumoniae (Spn) is the leading cause of pediatric complicated community-acquired pneumonia (cCAP), it is infrequently recovered by culture-based methods. We studied the real-world clinical impact of an Spn polymerase chain reaction (PCR) assay for pleural fluid. This pre-post quasi-experimental cohort study compared pathogen detection, antibiotic usage, and outcomes in children hospitalized with cCAP requiring pleural effusion or empyema drainage at Children's Hospital Colorado between 2016 and 2023. Patients were compared across 2 diagnostic periods: pre-Spn PCR and post-Spn PCR. Cox proportional hazard models compared time from admission to pathogen detection, optimal therapy (narrowest pathogen-directed or guideline-recommended empiric therapy), and methicillin-resistant Staphylococcus aureus (MRSA) therapy discontinuation between periods. Compared to the pre-Spn PCR cohort (n = 149), the post-Spn PCR cohort (n = 79) was more likely to have a pathogen detected (73.4% post-PCR vs 38.9% pre-PCR, P < .001), driven by more Spn detections (45.6% vs 14.1%, P < .001). Time to pathogen detection during hospitalization was shorter in the post-Spn PCR period (P < .001). The post-PCR cohort was more likely to receive optimal therapy (84.8% vs 53.0%, P < .001), with shorter median times to optimal antibiotics (4.9 vs 10.0 days, P < .001) and MRSA therapy discontinuation (1.5 vs 2.5 days, P = .03). There were no differences in hospital length of stay or readmissions. Spn molecular testing of pleural fluid in children with cCAP resulted in significantly more microbiologic diagnoses and was associated with the optimization of antibiotics and decreased exposure to MRSA therapy, suggesting its clinical impact for pediatric complicated pneumonia.

The epidemiology and management of spontaneous spinal epidural abscesses in children: a single-center experience.

Spinal epidural abscesses (SEAs) are rare infections in children but can lead to significant neurological sequelae. The authors sought to describe the presentation, management, and outcomes of children with these infections at their institution. This was a retrospective study of pediatric patients admitted with SEA to a quaternary children's hospital between 2013 and 2023. Clinical characteristics including laboratory, surgical, and antimicrobial data were collected and analyzed. Fourteen patients (median age 3.7 years) had SEAs. Thirteen (93%) patients developed the infection in the outpatient setting, and of these 10 (77%) were evaluated by a medical provider prior to the encounter when the diagnosis was made. The most common causative pathogen was Staphylococcus aureus. Thirteen (93%) of 14 patients underwent a surgical procedure, and patients were treated with antibiotics for a median of 38 days. Eleven (79%) of 14 patients received enteral antibiotics for part of their treatment course. All patients recovered with no neurological sequelae. SEAs are rare infections, but good outcomes can be obtained with prompt antimicrobial and surgical management. Enteral antibiotics should be considered as part of therapy. Larger multicenter studies are needed to determine the optimal antibiotic duration and route, and which patients should undergo neurosurgical intervention versus interventional radiology drainage or medical management alone.

An optimal antibiotic selection framework for Sepsis patients using Artificial Intelligence

In this work we present OptAB, the first completely data-driven online-updateable antibiotic selection model based on Artificial Intelligence for Sepsis patients accounting for side-effects. OptAB performs an iterative optimal antibiotic selection for real-world Sepsis patients focussing on minimizing the Sepsis-related organ failure score (SOFA-Score) as treatment success while accounting for nephrotoxicity and hepatotoxicity as serious antibiotic side-effects. OptAB provides disease progression forecasts for (combinations of) the antibiotics Vancomycin, Ceftriaxone and Piperacillin/Tazobactam and learns realistic treatment influences on the SOFA-Score and the laboratory values creatinine, bilirubin total and alanine-transaminase indicating possible side-effects. OptAB is based on a hybrid neural network differential equation algorithm and can handle the special characteristics of patient data including irregular measurements, a large amount of missing values and time-dependent confounding. OptAB’s selected optimal antibiotics exhibit faster efficacy than the administered antibiotics.

Therapy for Non-Diabetic Foot Infections After Orthopedic Foot and Ankle Surgery: The Duration of Post-Debridement Antibiotic Treatment Does Not Alter Failure Risk.

Despite growing numbers of scientific publications on the optimal antibiotic treatment for diabetic foot infections, the data on the adult population with non-diabetic (postsurgical) foot infections is limited. Therefore, one of the largest single-center databases at the Balgrist University Hospital in Zurich, Switzerland, was established between January 2014 and August 2022. Using a case-control study design, we retrospectively investigated failures of combined surgical and antibiotic therapy for surgical site foot infections (SSIs). Overall, 17.4% of the episodes experienced therapeutic failures, particularly in patients with infected ankle prostheses. However, age, biological sex, pathogens, the duration of post-debridement antibiotic treatment, the number of surgical debridements, or the use of negative-pressure wound care altered the failure risk. In the multivariate logistic regression analyses, the duration of postsurgical antibiotic use was completely indifferent (as a continuous variable with an odds ratio of 1.0 and a 95% confidence interval ranging from 0.96 to 1.03) when stratified into inter-tertiary groups. Our findings suggest that shorter courses of systemic antibiotics may be appropriate in non-diabetic adults, supporting better antibiotic stewardship. Ongoing randomized controlled trials are under way to investigate which patients might safely receive shorter antibiotic treatments for surgical site infections following elective foot and ankle procedures.

Monte Carlo simulation for dosage optimization of the best available therapy for bloodstream infections secondary to carbapenemase-producing Klebsiella pneumoniae in critically ill patients

ObjectiveWe aimed to use Monte Carlo simulation, based on pharmacokinetic/pharmacodynamic targets, to investigate and determine the optimal dosage of the available combination therapies for carbapenem-resistant Klebsiella pneumoniae (CRKP) in critically ill patients. MethodsWe collected CRKP clinical isolates from Phramongkutklao Hospital between October 2020 and June 2022. A molecular study of resistant genes was performed using polymerase chain reaction. Broth microdilution checkerboards were used to evaluate the mono- and synergistic antibiotic activities. Monte Carlo simulation was used to determine the optimal antibiotic regimens, based on the probability of target attainment (PTA) and cumulative fraction of response. ResultsThe 54 CRKP isolates were resistant to tigecycline (100%), colistin (75.9%), amikacin (70.4%), and gentamicin (63.0%). The most common carbapenemase genotype was blaoxacillinases (OXA)-48-like (42.6%), followed by blaNew Delhi metallo beta-lactamase (NDM) (29.6%) and coexistence of blaOXA-48-like and blaNDM (22.2%). Based on the PTA, synergistic and additive activities against CRKP isolates were observed with appropriate dosages of tigecycline–colistin (67.9%), tigecycline–gentamicin (62.2%), and tigecycline–amikacin (51.4%). ConclusionsTigecycline–colistin was the best available combination therapy for critically ill patients with CRKP, especially NDM. When used in combination with tigecycline, a colistin creatinine clearance of <90 mL/min can raise the cumulative fraction of response target and less nephrotoxicity.

Navigating antibiotic therapy in acute cholangitis: Best practices and new insights.

Globally, antibiotic resistance is linked to increased morbidity, mortality, and healthcare costs, which necessitates further research on optimal antibiotic usage. Acute cholangitis (AC), a common cause of community-acquired bacteremia, often requires antimicrobial therapy. Therefore, studying the appropriate use of antibiotics for AC is considered crucial for suppressing the emergence of resistant bacteria and reducing adverse antibiotic-associated events. The Tokyo Guidelines 2018 (TG18) recommend 4-7 days of antibiotics post-biliary drainage. However, this lacks strong evidence and is based primarily on various evidence and expert opinions. Recent retrospective studies advocate for a shorter 1-3-day antibiotic course for AC, thereby prompting a need to reassess the treatment duration to balance therapeutic efficacy and minimize resistance and adverse effects. Choosing the appropriate duration and antibiotics based on susceptibility to pathogens causing cholangitis is important. Awareness of local resistance patterns and understanding patients' risks of resistant pathogens are prerequisite for effective treatment. We must explore the applicability of these guidelines in specific scenarios such as severe AC, positive blood cultures, fever, or hilar biliary obstructions due to malignancy. This comprehensive review considers both the duration and type of antibiotics and aims to enhance treatment outcomes while reducing the risk of resistant bacterial infections.

Oral Azithromycin versus Oral Doxycycline in the Treatment of Meibomian Gland Dysfunction: A Systematic Review and Meta-Analysis.

The first-line treatment approach of Meibomian gland dysfunction (MGD) comprises conservative management, but antibiotics with anti-inflammatory properties are recommended in severe or persistent cases. Oral doxycycline and oral azithromycin are commonly used antibiotics for managing MGD. However, a systematic review and meta-analysis comparing their efficacy and safety is needed. This study adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and included randomized controlled trials (RCTs) focusing on patients with MGD. The primary outcomes assessed were symptom score, sign score, and overall clinical response. Adverse events were also evaluated. Multiple databases were comprehensively searched, and data extraction and quality assessment were performed by two independent authors. Four trials and a quasi-experimental study involving 612 participants/eyes were included. Meta-analysis showed a statistically significantly lower mean sign score in the oral azithromycin group than in the doxycycline group. However, one RCT reported a lower mean symptom score in the doxycycline group. No significant differences were found in the means of total scores between the two groups. Systemic adverse events such as nausea, abdominal cramps, decrease in appetite, and diarrhea were more prevalent in the doxycycline group. The systematic review and meta-analysis suggest that oral azithromycin may be more effective in reducing signs of MGD than oral doxycycline. However, the results regarding symptom scores and total scores were inconclusive. Azithromycin also demonstrated a better safety profile with fewer gastrointestinal adverse events. Further research is needed to determine the optimal antibiotic treatment for MGD.

Impact of rapid blood culture identification PCR panel on optimal antibiotic use in methicillin-susceptible Staphylococcus aureus bacteremia.

In this retrospective study of 200 patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, the implementation of the BioFire® blood culture identification polymerase chain reaction (PCR) panel was associated with a decreased time to optimal MSSA antibiotic therapy and shorter durations of empiric anti-MRSA antibiotic therapy and bacteremia. The findings demonstrate the significant role of rapid PCR testing and routine stewardship review in optimizing antimicrobial therapy and management of MSSA bacteremia.

The optimal antibiotic treatment duration for community-acquired pneumonia in adults diagnosed in general practice in Denmark (CAP-D): an open-label, pragmatic, randomised controlled trial

BackgroundUse of antibiotics is the main driver of antimicrobial resistance which is considered one of the biggest threats to human health. In Denmark, most antibiotics are prescribed in general practice. Acute lower respiratory tract infections, including community-acquired pneumonia (CAP), are among the most frequent indications for antibiotic prescribing. Phenoxymethylpenicillin is established as first-line treatment in general practice in Denmark. However, the treatment duration with phenoxymethylpenicillin is mostly based on traditions. Both 5 and 7 days of treatment is recommended in Danish guidelines, and when asking the general practitioners about what treatment duration, they prescribe the variation is even bigger. Several hospital-based studies have proven short course (≤ 6 days) antibiotic treatment non-inferior to long course (≥ 7 days) treatment of CAP. No evidence exists on the optimal treatment duration for CAP in non-hospitalised patients.This randomised controlled trial aim to investigate the optimal treatment duration with phenoxymethylpenicillin for CAP in adults diagnosed in general practice in Denmark.MethodsThis is an open-label, pragmatic, randomised controlled, five-arm DURATIONS trial. Participants will be recruited from at least 24 general practices in Denmark. Eligible participants are adults, with no pre-existing lung disease, presenting with symptoms of CAP, and in whom the general practitioner finds it relevant to treat with antibiotics. The study will compare treatment with phenoxymethylpenicillin 1.2 MIE q.i.d. in 3, 4, 5, 6, and 7 days.DiscussionThis study will provide evidence for the optimal antibiotic treatment duration of CAP in general practice and inform future guidelines on CAP in all countries using phenoxymethylpenicillin for the treatment of acute respiratory tract infections in adults. The results of this study might also be used to guide treatment recommendations in other countries using phenoxymethylpenicillin.Moreover, a (potential) reduction in antibiotic use might lower the development of antimicrobial resistance, increase patient treatment adherence, reduce risks of adverse events, and lower the economical expTrial registrationClinicalTrials.gov: NCT06295120. Registered 28 February 2024. The Scientific Ethics Committee for the North Denmark Region: N-20230039.

Getting rapid diagnostic test data into the appropriate hands by leveraging pharmacy staff and a clinical surveillance platform: a case study from a US community hospital

Abstract Objectives To outline the procedural implementation and optimization of rapid diagnostic test (RDT) results for bloodstream infections (BSIs) and to evaluate the combination of RDTs with real-time antimicrobial stewardship team (AST) support plus clinical surveillance platform (CSP) software on time to appropriate therapy in BSIs at a single health system. Methods Blood culture reporting and communication were reported for four time periods: (i) a pre-BCID [BioFire® FilmArray® Blood Culture Identification (BCID) Panel] implementation period that consisted of literature review and blood culture notification procedure revision; (ii) a BCID implementation period that consisted of BCID implementation, real-time results notification via CSP, and creation of a treatment algorithm; (iii) a post-BCID implementation period; and (iv) a BCID2 implementation period. Time to appropriate therapy metrics was reported for the BCID2 time period. Results The mean time from BCID2 result to administration of effective antibiotics was 1.2 h (range 0–7.9 h) and time to optimal therapy was 7.6 h (range 0–113.8 h) during the BCID2 Panel implementation period. When comparing time to optimal antibiotic administration among patients growing ceftriaxone-resistant Enterobacterales, the BCID2 Panel group (mean 2.8 h) was significantly faster than the post-BCID Panel group (17.7 h; P = 0.0041). Conclusions Challenges exist in communicating results to the appropriate personnel on the healthcare team who have the knowledge to act on these data and prescribe targeted therapy against the pathogen(s) identified. In this report, we outline the procedures for telephonic communication and CSP support that were implemented at our health system to distribute RDT data to individuals capable of assessing results, enabling timely optimization of antimicrobial therapy.