Days Of Antibiotics Research Articles

Time of Attainment of Clinical Remission and Peripheral Blood Count Recovery during Induction Chemotherapy for Childhood Acute Lymphoblastic Leukemia

Background: Acute lymphoblastic leukemia(ALL) is the most common pediatric malignancy. Infection and bleeding are the leading cause of death during induction chemotherapy in childhood ALL. So, proper knowledge about anticipated infection and bleeding are very important during this period. But the duration of clinical remission and recovery of peripheral blood count during induction chemotherapy is not well reported in literature. Objective: The aim of the study was to determine the time of attainment of clinical remission and recovery of peripheral blood count after initiation of induction chemotherapy and to determine if the duration of clinical remission and peripheral blood count recovery differs between therapeutic risk groups. Methods: This prospective observational study was conducted from January 2021 to December 2021 in the Department of Paediatric Haematology and Oncology, BSMMU. Newly diagnosed admitted Eighty-Six ALL of both sexes aged 1 to 17.9 years were included. After commencing chemotherapy, physical examination was recorded every day until clinical remission and complete blood count (CBC) was recorded one to two days interval until peripheral blood count recovery. The number of packed red blood cell (PRBC) and platelet transfusions and the number of days of intravenous antibiotics were recorded. Results: Mean duration of clinical remission, complete Hemoglobin (Hb), Absolute neutrophil count(ANC) and platelet recovery was 8.4 ± 4.5 days, 25±7.9 days, 23.3±5.6 days and 21.8±6.4 days respectively (p<0.01). Time to attain partial recovery of platelet was 14.0±4.9 days in high risk and 19.2±5.3 days in standard risk group. PRBC transfusion requirement was 2.2±1.2 units in high risk group and 1.7±0.8 units in standard risk group (p<0.05). Time to attain partial recovery of ANC, number of days with I/V antibiotics and duration of treatment interruption were higher in high risk group. Conclusion: Time of clinical remission was similar between risk group. Platelet recovery occurred earlier than Hemoglobin (Hb) and absolute neutrophil count (ANC) recovery. Transfusion and supportive care requirement were more in high risk group during induction chemotherapy. So, more supportive care should be arranged up to three weeks of induction period to increase survival of high risk childhood ALL. Bangladesh Med Res Counc Bull 2023; 49: 177-182

Is Short-Course Antibiotic Therapy Suitable for Pseudomonas Aeruginosa Bloodstream Infections in Onco-Hematology Patients with Febrile Neutropenia? Results of a Multi-Institutional Analysis

Background. Several studies have suggested that short-course antibiotic therapy does not increase infection recurrence or mortality in immunocompetent patients. While similar studies in patients with hematological malignancies were rare. Methods. This cohort included onco-hematology patients with Pseudomonas aeruginosa (PA) bloodstream infections (BSI). These patients had undergone chemotherapy or hematopoietic stem cell transplantation (HSCT) and experienced febrile neutropenia. Inverse probability of treatment weighting was used to balance the confounding factors. Results. 434 patients met eligibility criteria (short-course, 7-11 days, n=229; prolonged therapy, 12-21 days, n=205). In the weighted cohort, after multivariate analysis, the recurrent PA infection at any site or mortality within 30 days of completing therapy occurred in 8 (3.9%) patients in the short-course group and in 10 (4.9%) in the prolonged-course group ( p = 0.926), the recurrent infection within 90 days occurred in 20 (9.8%) patients in the short-course group and in 13 (6.3%) patients in the prolonged-course group ( p =0.276), and the recurrent fever within 7 days occurred in 17 (8.3%) patients in the short-course group and in 15 (7.4%) in the prolonged-course group ( p = 0.980). While multidrug-resistant PA, relapsed/refractory hematological malignancies and perianal mucositis were the key determinants of infection recurrence/mortality other than the short course of antibiotic treatment (p<0.05 for all). On average, patients who received short-course antibiotic therapy spent 3.3 fewer days in the hospital ( p<0.001). Conclusions. We found that onco-hematology patients with PA BSI who received approximately 8 days of antibiotics had similar clinical outcomes to those who received a prolonged-course therapy, with the potential added benefit of earlier hospital discharge.

Infectious and Non-Infectious Pulmonary Complications in HCT Patients Treated with Post Transplant Cyclophosphamide (PTCy) Based Gvhd Prophylaxis

Introduction: Pulmonary complications are a leading cause of mortality and morbidity amongst pts undergoing hematopoietic stem cell transplantation (HCT). Increasingly, allogeneic HCT recipients are undergoing HCT with PTCy based GVHD prophylaxis. While lower rates of severe GVHD has been reported with PTCy, increased infection and organ toxicity has also been seen compared with standard calcineurin inhibitor (CNI) prophylaxis. The incidence and outcomes of pulmonary complications, both infectious and non-infectious/immune in pts receiving PTCy remain poorly characterized. Therefore, we aimed to assess for these in this study. Methods: We performed a retrospective review of pts between 2012-2022 who underwent 1st allogeneic BMT and received PTCy as part of GVHD prophylaxis. We identified pts requiring hospitalization for pulmonary complications. Infectious cases were categorized as bacterial, fungal, viral, or mixed. Bacterial pneumonia was defined as fever, cough, dyspnea, purulence sputum, and new or progressive radiographic evidence of infiltrate not explained by a non-infectious cause, treated with at least 5 days of antibiotics. Viral and fungal pneumonia were diagnosed based on identified organism. Noninfectious complications included idiopathic pulmonary syndrome (IPS), diffuse alveolar hemorrhage (DAH), cryptogenic organizing pneumonia (COP), and bronchiolitis obliterans syndrome (BOS). IPS was defined as radiographic evidence of alveolar infiltrates, dyspnea, cough, increased work of breathing or oxygen requirements, exclusion of infection or alternate pathology, and treated with high-dose systemic corticosteroids. DAH was defined as radiographic evidence of widespread alveolar injury, increased work of breathing or oxygen requirements, and persistent and progressive bloody return on BAL. COP was defined as pathologic evidence of organizing pneumonia on transbronchial lung biopsy in the absence of pathogens. BOS was defined as FEV1/FVC <0.7 and FEV1 <75% with a ≥10% decline over <2 years. Results: A total of 224 pts were identified. Median age at HCT was 55 years (20-78) (Table 1). 138 (64%) were male. The median comorbidity index (HCT-CI) score was 3 and median Karnofsky Performance Score was 80. 56%(n=125) pts underwent HCT with nonmyoablative conditioning, 78% (n=157) underwent HCT with a haploidentical donor, and 65% (n=145) of grafts were peripheral blood. 4%(n=10) were current smokers at time of HCT, 38% (n=84) were former smokers. 16% (n=35) had an existing diagnosis of asthma or COPD. 72 (32%) pts were hospitalized for pneumonia at any point after HCT. There were 23 bacterial pneumonias (30%), 20 viral (27%), 13 fungal (18%), and 12 were mixed (17%) (Table 2). There were 4 pts (6%)with documented pneumonia of unknown etiology due to rapid progression to death or hospice. 10 pts (4%) developed IPS with a median onset of 153 days (20-354). 2 pts (1%) developed COP with a mean onset of 754 days (388 - 1119). 5 pts (2%) developed BOS with a median onset of 336 days (153-677). 8 pts (4%) developed DAH with a median onset of 48 days (20-152). Among all patients, 57 pts (25%) required mechanical ventilation at any point post-HCT, and 18 pts (8%) were prescribed home oxygen at any point post-HCT. Overall, 80pts (77%) died due to non-relapse causes. 29 deaths (28%) were pulmonary related, (21 (20%) infectious and 8 (8%) noninfectious). Of the noninfectious pulmonary deaths, 3 pts died due to IPS, and 5 died due to DAH. Conclusion: In our cohort of pts receiving PTCy based GVHD prophylaxis, significant infectious pulmonary complications were common and were fatal in 9.4% of pts. Infections were the major driver of pulmonary related mortality, however, we observed noninfectious/immunologic pulmonary complications at a rate within or only slightly below the previously reported ranges among transplanted pts predominantly receiving CNI based prophylaxis.

1213. Application of Short Course Criteria for Community-Acquired Pneumonia (CAP) Among Patients Admitted Within a 17-community Hospital Telehealth Antimicrobial Stewardship Program (Tele-ASP)

Abstract Background A recent randomized controlled trial by Dinh et al. found three days of antibiotics was appropriate for certain community-acquired pneumonia (CAP) patients, but the real-world applicability of this study remains to be evaluated. In February 2022, a telehealth antimicrobial stewardship program (Tele-ASP) intervention was implemented across 17 small community hospitals to identify patients meeting clinical stability criteria used by Dinh et al. for short course therapy (3 days). An alert was implemented to notify the infectious diseases telehealth (Tele-ID) pharmacist of patients on room air for whom an antibiotic was ordered for pneumonia. Methods This IRB-approved study aimed to evaluate feasibility and impact of the intervention. Patients with severe or complicated CAP, known immunosuppression, or who were transferred were excluded. The primary outcome was total antibiotic duration. Secondary outcomes included whether the total duration was greater than 5 and 7 days and total IV antibiotic duration. Continuous antibiotic duration endpoints were assessed using Mann Whitney U and Fisher's Exact tests were used for categorical endpoints. Results Of 480 patients screened, only 148 (31%) patients met early clinical stability criteria. The primary reason for not meeting criteria was requirement of supplemental oxygen on Day 3 or greater on antibiotics (n=145). This proportion is far lower than previous studies, including that by Dinh et al., which found 60-70% patients met stability criteria. Of the 90 patients included, 27 patients had a Tele-ID review. Patients with an intervention were less likely to receive > 5 days of antibiotics (59% vs 73%) and > 7 days of antibiotics (19% vs. 32%), although these differences were not statistically significant. Conclusion This study relied on accuracy of oxygen charting, which may partly explain relatively lower proportion of patients meeting strict clinical stability criteria and likely limits feasibility of a scalable intervention. A pragmatically modified approach for this Tele-ASP intervention (i.e. allowance for no more than 1 unmet criterion) is an important area for further exploration and could improve the feasibility of a scalable telehealth intervention. Disclosures All Authors: No reported disclosures

2944. Comparative Effectiveness and Safety of 5-7 days versus 10 days of Antibiotics for Acute Bacterial Sinusitis in Children

Abstract Background Acute bacterial sinusitis accounts for 5 million pediatric antibiotic prescriptions in the United States each year, with 65% amoxicillin or amoxicillin-clavulanate. More than 90% of pediatric patients are prescribed 10+ days of antibiotics. No study has compared shorter to longer treatment. This study compares 5-7 days versus 10 days of treatment in children and adolescents. Methods This cohort study included patients < 18 years with an outpatient encounter for acute sinusitis and a same-day dispensation of either a 5–7 day supply or a 10 day supply of amoxicillin or amoxicillin-clavulanate between January 1, 2017 and December 31, 2020 in the MarketScan Commercial Claims and Encounters database. Treatment failure, defined as a new antibiotic dispensation, an ED or inpatient encounter for acute sinusitis, or an inpatient complication of acute sinusitis, was assessed in the first 5, 10, and 30 days after cohort entry. Adverse and control outcomes were captured. We used Cox proportional hazards regression with propensity score (PS) overlap weights for confounding control. Results The initial cohort included 254,629 patients, among which 19,627 patients were prescribed a 5-7-day treatment (exposure) and 235,002 patients were prescribed a 10-day treatment (referent). After PS overlap weighting, groups were balanced on all measured covariates (Table 1). The rate of 30-day treatment failure was 167.77 per 1,000 person-years (95% CI, 155.94, 180.49) among patients dispensed 5-7 days of treatment and 150.19 per 1,000 person-years (95% CI, 145.54, 154.99) among patients dispensed 10 days of treatment (hazard ratio 1.12 [95% CI, 1.03,1.21]) (Table 2). Adverse events were rare, and there was no difference between groups in a negative control outcome (Table 3).Table 1:Patient and treatment characteristicsTable 2:Treatment FailureTable 3:Adverse and control outcomes Conclusion The absolute risk of treatment failure was very low. Children and adolescents dispensed 5-7 days of antibiotic treatment had a slightly higher rate of treatment failure compared to 10 days of antibiotic treatment. Adverse effects were rare, with a potentially lower rate of yeast infections following shorter treatment. The marginal benefit and increased risk of side effects with longer treatment indicates that shorter treatment of acute bacterial sinusitis, 5-7 days, may be a reasonable initial approach in some populations. Disclosures Timothy J. Savage, MD, MPH, MSc, UCB: Contract to Brigham and Women's Hospital Krista F. Huybrechts, PhD, MS, Takeda: Grant/Research Support|UCB: Grant/Research Support

1664. The Impact of Levofloxacin Prophylaxis on Empiric Intravenous Antibiotic Use in Pediatric Hematopoietic Stem Cell Transplant Recipients

Abstract Background Clinical trials have demonstrated that levofloxacin prophylaxis during periods of neutropenia in hematopoietic stem cell transplantation (HSCT) reduces the frequency of bacteremia in adults and febrile episodes in children. Therefore, levofloxacin prophylaxis may also have a role in reducing empiric intravenous antibiotic (EIA) use. Methods This retrospective review assessed the impact of levofloxacin prophylaxis for patients < 18 years undergoing HSCT at a Canadian children’s hospital. The primary outcome was antibiotic days of therapy (DOT) during the pre-engraftment period comparing the pre-levofloxacin era (Jan 1, 2019–Jun 30, 2020) to the levofloxacin era (Jul 1, 2020–Dec 31, 2021). Patients were excluded if they were receiving EIA at the time of transplant, received chimeric antigen receptor T-cell therapy, or if levofloxacin use was discordant with their era. Secondary outcomes included the number of positive blood cultures and clinical deterioration episodes (clinical change resulting in blood culture draw and initiation/change of EIA). Results Fifty-four of 152 patients (36.5%) and 55 of 147 patients (37.4%) were included in the pre-levofloxacin and levofloxacin eras respectively. The most common reasons for exclusion were EIA use at the time of transplant and levofloxacin use discordant with the patient's era (Figure 1). Baseline characteristics were not significantly different between groups (Table 1). Mean DOT/pre-engraftment days (%) were significantly lower in the levofloxacin era for piperacillin-tazobactam (53.3 vs. 38.3, p=0.004) and amikacin (1.7 vs. 0.1, p=0.03), while there was no significant difference for meropenem, vancomycin, or all other antibiotics combined. There was also no significant difference in the number of positive blood cultures (11 vs. 7, p=0.35) or clinical deterioration episodes (55 vs. 66, p=0.1). Conclusion Levofloxacin prophylaxis in children undergoing HSCT reduced percent pre-engraftment days on piperacillin-tazobactam and amikacin, with no significant impact on the number of positive blood cultures or clinical deterioration episodes. Therefore, levofloxacin prophylaxis may facilitate antimicrobial stewardship activities through reduced use of certain broad-spectrum antibiotics. Disclosures Kathryn E. Timberlake, PharmD, Avir Pharma: Advisor/Consultant

91. Implementation of a blood culture algorithm in emergency department patients as a diagnostic stewardship intervention

Abstract Background Blood cultures (BCx) are commonly ordered for patients at low risk of bacteremia. Liberal ordering can increase false-positive results due to contamination, along with increasing length of stay, excess antibiotics, and unnecessary diagnostic procedures. We implemented an algorithm for appropriate blood culture obtainment (Figure 1) in an academic tertiary care emergency department (ED) and assessed the intervention’s impact on various operational, clinical, and safety metrics.Figure 1:ED Blood culture algorithm Methods We performed a prospective cohort study in the Duke University Hospital ED from 12/2022 to 3/2023 using historical controls from 12/2020-11/2022. The BCx algorithm was disseminated in-person, electronically, and accessible online. Weekly chart review of all eligible patients for algorithm adherence was completed by 7 ED clinicians with monthly feedback provided to all ED providers. We defined a BCx event as 1 or more BCx sets within 24 hours. We excluded patients < 18 years, absolute neutrophil count < 500 109/L, and heart and lung transplant recipients. We measured BCx order volume, indication, algorithm adherence, BCx positivity rate, antibiotic days of therapy (DOT), and 30-day hospital readmission. Results Average monthly BCx volume was 1387 pre-intervention compared to 1226 post-intervention (p= 0.046). An increase in culture positivity was see post-intervention with a rate of 13.9% compared to 11.23% in the pre-intervention group (Figure 2, p< 0.001). The majority of the 2168 BCx adhered to the algorithm. (Figure 3). The most common reasons for non-adherence were isolated fever or leukocytosis (29%), non-severe community-acquired pneumonia or healthcare-associated pneumonia (6.9%) and non-severe cellulitis (4%). No change in DOT (786 vs. 783 days of therapy per 1000 patient days, p-value 0.85) (Figure 4) or monthly 30-day hospital readmission (21.1% vs 19.6%, p-value 0.30) was observed.Figure 2:Blood cultures drawn per month and % appropriate pre/post-intervention (N=2168)Figure 3:Algorithm Adherent vs. Algorithm Non-Adherent blood cultures per month (N=2168)Figure 4:Emergency Department anti-bacterial days of antibiotic therapy per 1000 patient days Conclusion Introduction of a BCx algorithm in an academic tertiary care ED, resulted in a decrease in BCx volume, increase in BCx positivity rate, and no increase in DOT or readmission was observed. (Table 1)Table 1:Blood culture volume, positivity rate, days of antibiotic therapy, and 30-day readmission Disclosures Jessica Seidelman, MD, MPH, Uptodate: content editor for pelvic osteomyelitis page

1189. The Impact of Clinical Staff Pharmacist Driven Weekend Antimicrobial Stewardship Coverage in a Quaternary Hospital in UAE

Abstract Background Pharmacy antimicrobial stewardship services were extended to cover the weekends, incorporating a clinical staff pharmacist with infectious disease (ID) training to cover antimicrobial stewardship program (ASP) activities on weekends is an opportunity. The aim of this study is to assess the impact of integration ASP clinical staff pharmacist into an ASP on weekends by collecting and analyzing the documented pharmacists’ ASP interventions before and after implantation of the service. Methods A single center, pre-post quasi-experimental study. Data were collected retrospectively from the electronic medical record (EMR). The study included at 2 sets of data: pre-implementation (2020) and post-implementation (2021) of an ASP weekend pharmacist, The primary outcome is to evaluate pharmacist ASP Interventions through prospective audit and feedback review analysis. Secondary outcomes include antibiotics days of therapy (DOT), length of hospital stay (LOS), healthcare associated Clostridioides difficile infection (CDI) and infection-related readmission.Table 1:Characteristics of the pre-and post-intervention group Results During the study, an increase in the number of documented interventions was observed with 452 interventions were documented on 362 patients during the post-implementation period compared to 114 interventions were documented on 108 patients during the pre-implementation period (p = 0.04). A reduction in the LOS was observed with a median (IQR) of 16 days (8-34) during the post-implementation period compared to 27.5 days (10-56) during the pre-implementation period (p = 0.001), while the median (IQR) total DOT was increased during the post-implementation period 8 (6-11) versus 7 (4-11) during the pre-implementation period (p = < 0.001). No differences were observed in healthcare associated Clostridioides difficile infection (CDI) and infection-related readmission.Table 2:Pharmacist interventions on the pre-and post-intervention groupTable 3:Outcome of pharmacists driven weekend antimicrobial stewardship on the pre-and post-intervention group Conclusion The pharmacists driven weekend antimicrobial stewardship is an opportunity for the pharmacists to intervene and optimize patients’ treatment plan and contributed towards a significant shortened length of hospital stay. Therefore, healthcare facilities should prioritize the involvement of pharmacists in weekend ASPs to ensure consistent, high-quality care throughout the week. Disclosures All Authors: No reported disclosures

2438. Positive Cerebrospinal Fluid Cultures from Intraventricular Reservoirs for CLN2 Patients: One Institution's Experience

Abstract Background Enzyme replacement therapy (ERT) with cerliponase alfa (Brineura) has been shown to slow progression of milestone deterioration in Neuronal Ceroid Lipofuscinosis Type 2 (CLN2), an inherited neurodegenerative lysosomal storage disorder. Brineura must be administered intraventricularly every 2 weeks, necessitating the placement of ventricular reservoirs and requiring frequent access. Traditionally, positive cerebrospinal fluid (CSF) cultures are managed with device replacement and antibiotic treatment. We sought to establish which circumstances might allow for careful observation without device removal. In this study, we report our single-institution experience with clinical outcomes of positive CSF cultures in 16 CLN2 patients over 6 years. Methods We retrospectively reviewed a cohort of 16 patients with CLN2 disease who had ventricular reservoirs placed for ERT administration. At each ERT infusion, CSF was collected by sterile technique and cultured by both thioglycolate broth and agar plate. Epidemiologic and microbiologic data, symptomatology, total antibiotic days, removal and replacement of ventricular reservoir, hospital length of stay, and mortality were analyzed for each patient. Results In our cohort, 11 of 16 patients (69%) had at least one positive CSF culture (Fig 1). Of the 11 with positive cultures, only 3 had their device removed and replaced for a positive culture with concurrent antibiotic treatment at our center, and 2 patients subsequently have been treated with prophylactic antibiotics at infusions (Fig 2). Out of 1401 total CSF cultures, 64 (4.56%) were positive. The most common organism grown was Cutibacterium acnes, which typically grew in only broth culture (82%), suggesting low bacterial burden (Fig 3). The other 7 patients with positive cultures remained asymptomatic with no intervention required. Conclusion At our institution, we have found that in asymptomatic patients with frequently accessed ventricular reservoirs, positive CSF culture with low virulence skin flora was common, and rarely required intervention. This strategy reduced the risks of invasive surgery, prolonged antibiotic courses, and missed infusions. In the future, routine screening cultures in asymptomatic patients can be avoided. Disclosures Raymond Wang, MD, Biomarin Pharmaceutical: Advisor/Consultant|Biomarin Pharmaceutical: Grant/Research Support|Biomarin Pharmaceutical: equity interest Antonio C. Arrieta, MD, FIDSA, FPIDS, Astellas Pharma Global Development, Inc.: Advisor/Consultant|Astellas Pharma Global Development, Inc.: Grant/Research Support|Astellas Pharma Global Development, Inc.: Honoraria|Cumberland Pharmaceutical: Grant/Research Support|IDbyDNA: Advisor/Consultant|IDbyDNA: Grant/Research Support|Melinta: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Nabriva: Grant/Research Support|Paratek Pharmaceuticals: Grant/Research Support|Pfizer, Inc: Advisor/Consultant|Pfizer, Inc: Grant/Research Support|Roche/Genentech: Grant/Research Support|The Medicine Company: Grant/Research Support

2270. Dealing with an old foe –Assessment of Knowledge, Attitude, and Practices: A survey on management of Staphylococcus aureus bacteraemia among Indian Physicians

Abstract Background Staphylococcus aureus bacteraemia (SAB) is associated with high morbidity, mortality, and healthcare costs. Effective management of SAB significantly improves outcome. There is significant gap in the guidelines and clinical practice. This survey was conducted with aim to assess opinions and practice patterns in management of SAB among Indian clinicians. Methods We conducted a cross-sectional respondent-driven survey, using a 45-item, anonymous, voluntary, multiple-choice google form questionnaire among clinicians in India, after obtaining ethical approval from the institute. We distributed survey via social media, WhatsApp, and E-mail. Survey responses were analysed using SPSS, Version 25.0. Results The total of 125 practicing clinicians responded to this survey. Questions where systematically divided into treatment of choice for MSSA, MRSA, additional investigations, persistent bacteraemia, and adjunctive anti-toxin therapy. Around 57% of the respondents have 1-10 episodes of SAB every month. For suspected SAB, most respondents (74%) preferred vancomycin as empiric therapy. If MSSA was identified, 66.7% initiated on Anti staphylococcal penicillin, while in MRSA vancomycin was selected by majority (80%) (Figure 1 & 2). Most clinicians (74%) perceived 1st generation cephalosporins non-inferior to ASPs. Infectious diseases referral for SAB was undertaken in only in about 56% of the cases, with 25% respondents citing non-availability of ID specialist in the institute. Repeat blood cultures and echocardiography was performed by most respondents. Lack of consensus was apparent in diagnosis and management of persistent bacteraemia and oral switch of therapy (Figure 1 & 2).Most respondents managed SAB with at least 14 days of parenteral antibiotics in several scenarios. But, in patients with complicated SAB there was significant practice variation (Figure 3). Figure - 1 Drug of choice in MSSA, MRSA and management of persistent bacteraemia according to the respondents Figure 2 Persistent bacteraemia definition according to the respondents along with the additional tests performed Conclusion There were some areas of consensus, but this survey highlights considerable practice variation among clinicians. Although the value of ID consultation in SAB management has been established by multiple studies, this survey demonstrates that there remains ample opportunity to further define best practices and optimize management of this complex disease. Disclosures All Authors: No reported disclosures

Association Between Common Empiric Antibiotic Regimens and Clostridioides Difficile Infection in Pediatric Appendicitis

BackgroundClostridioides Difficile Infection (CDI) is a serious antibiotic related complication that has been reported among children undergoing treatment of appendicitis. CDI likelihood amongst different empiric antibiotic regimens for appendicitis remains unclear but likely has important implications for antibiotic stewardship. MethodsA retrospective cohort study of the Pediatric Health Information System was used to examine patients ages 1 through 18 who received operative management of acute appendicitis. Common empiric antibiotic regimens 1) Ceftriaxone & Metronidazole (CM) 2) Piperacillin & Tazobactam (PT) and 3) Cefoxitin were compared. Study outcomes were CDI within 28 days post-appendectomy and 30-day post-appendectomy percutaneous drainage procedures. Subset analyses were repeated to only include hospitals that standardized empiric antibiotic choice. ResultsOf 105,911 patients, 220 (0.21 %) developed CDI. CDI was more common in patients that received CM (CM 0.29 % vs PT 0.15 % vs Cefoxitin 0.18 %; P < 0.01). On adjusted analysis, PT was associated with a lower likelihood of CDI (OR, 0.48; 95%CI, 0.31–0.74) compared to CM which was consistent in hospitals with standardized antibiotic choice. Exposure to more unique antibiotic regimens (OR, 1.70; 95 % CI, 1.50–1.93) and higher total antibiotic days (OR, 1.17; 95 % CI 1.13–1.21) were associated with an increased likelihood of CDI. There was no significant difference in the likelihood of post-appendectomy percutaneous drainage between antibiotic regimens. ConclusionsCDI is rare following appendectomy for pediatric appendicitis. While PT was associated with statistically lower rates of CDI compared to CM, antibiotic stewardship efforts to avoid mixed regimens and decrease overall antibiotic exposure warrant exploration. Level of EvidenceLevel III.

Severe acute urticaria is associated with elevated plasma levels of D-dimer.

Evaluation of the disease severity of acute urticaria (AU) is essential for adequate treatment of patients. However, there are no reliable biomarkers for such an evaluation. In our department, we observed patients with severe AU having elevated plasma D-dimer levels. Thus, the objective of this study was to investigate the elevated D-dimer levels in patients with severe AU in more detail. One hundred and thirty-nine hospital patients diagnosed with severe AU were enrolled. Clinical laboratory data were collected from electronic medical records. One hundred and seventeen of the patients presented with elevated plasma D-dimer levels. Compared to the normal group, the elevated group had a significantly higher proportion of patients who were female, younger, febrile, and had a shorter prehospital time (P < 0.05). Univariate regression analysis showed that neutrophil percentage, C-reactive protein (CRP), and lactate dehydrogenase (LDH) levels increased as D-dimer levels increased, while prehospital time showed the opposite trend. Multiple regression analysis was used to estimate the simultaneous effects of CRP and LDH on D-dimer levels. Patients who responded to additional antibiotic treatment had higher levels of D-dimer. The group with highly elevated D-dimer levels required a higher maximum dose of daily glucocorticoids (GCs) to control the symptoms of AU. In conclusion, patients with severe AU might have elevated plasma D-dimer levels, which are positively correlated with CRP and LDH levels. Patients with severe AU with dramatically elevated D-dimer levels might need a higher dose of daily GCs and antibiotics to relieve symptoms. D-dimer may be a reasonable marker to evaluate the severity of AU and guide treatment.

Extended antibiotic therapy is associated with a lower rate of clinically relevant postoperative pancreatic fistula after pancreatoduodenectomy in intermediate- and high-risk patients: A single-institution analysis

BackgroundClinically relevant postoperative pancreatic fistula remains a common complication after pancreatoduodenectomy. The fistula risk score is a validated tool to predict the risk of clinically relevant postoperative pancreatic fistula. To mitigate complications, we have implemented an extended antibiotic pathway for patients at increased risk of clinically relevant postoperative pancreatic fistula (fistula risk score ≥3). We report outcomes after pancreatoduodenectomy in patients at increased risk for clinically relevant postoperative pancreatic fistula who received extended antibiotic therapy compared to those who received standard perioperative antibiotics (single dose before incision). MethodsSingle-institution analysis of 87 patients who underwent elective pancreatoduodenectomy (2018–2022) with soft gland texture and fistula risk score ≥3 and were treated with (n = 34) or without (n = 53) 10 days of broad-spectrum antibiotics (piperacillin/tazobactam converted to amoxicillin/clavulanic acid at discharge) after surgery. Associations between extended antibiotics and postoperative outcomes were analyzed. ResultsBaseline clinicodemographic factors were similar between cohorts. Patients who received extended antibiotics had shorter index days (6 vs 8 days, P = .004) and 90-day composite length of stay (8.5 vs 12 days, P = .018). Patients who received extended antibiotics had lower rates of clinically relevant postoperative pancreatic fistula (11.8% vs 37.7%; odds ratio = 0.17, 95% confidence interval: 0.04–0.68), wound infections (8.8% vs 30.2%; odds ratio = 0.08, 95% confidence interval: 0.01–0.50), organ space infections (14.7% vs 43.4%; odds ratio = 0.15, 95% confidence interval: 0.04–0.52), and image-guided drain placement (8.8% vs 34.0%; odds ratio = 0.15, 95% confidence interval: 0.04–0.62). There were no Clostridium difficile infections in the extended antibiotic group. ConclusionExtended antibiotic therapy is associated with a lower rate of clinically relevant postoperative pancreatic fistula and associated complications after pancreatoduodenectomy in patients with a fistula risk score ≥3. These results form the basis of a randomized controlled trial (NCT05753735).

Randomized control trial on impact of clinical pharmacist led interventions on antibiotic stewardship program in children 0 to 18 years age in a tertiary care hospital in southern India

A prospective randomized controlled interventional study was conducted at a quaternary care multispecialty hospital in South India with the primary objective of identifying opportunities to improve antibiotic prescribing patterns in neonates, children, and adolescents. The hospital has a robust clinical pharmacist program wherein antibiotic prescriptions were checked for appropriateness of antibiotic dose, route, formulation, duration of therapy, and IV to oral switch. These characteristics of antibiotic use were therefore similar in the 75 children in the control and 75 in the intervention group. The additional clinical pharmacist interventions analyzed in this study included checking if a provisional diagnosis had been made before initiating antibiotics, ensuring that appropriate cultures were sent before starting antibiotics, time taken to optimize antibiotic therapy in accordance to the culture sensitivity report and whether the indication for antibiotics use was as per Indian Acdemy of Pediatrics (IAP) Drug Formulary recommendations. The main outcomes were that all these parameters except the first (all children had a clinical diagnosis before initiating antibiotic/s) were better in the intervention group and there was a significant reduction in the total antibiotic days, an increase in antibiotic-free days, and an improvement in the appropriateness of duration of antibiotic therapy and frequency of the antibiotic dosing. However, since the incidence of severe sepsis was higher in the intervention group, broad-spectrum and restricted antibiotics were used, and thus treatment costs were higher in this group. The results indicate that despite already existing clinical pharmacist interventions, additional ones could further improve antibiotic prescription accuracy significantly; and re-emphasized the need to employ trained pediatric general and subspecialty clinical pharmacists in sufficient numbers to implement a successful pediatric antibiotic stewardship program in a hospital.

SPONTANEOUSREMOVALOFPLACENTAORMANUALREMOVALOFPLACENTA:WHICHISMOREBENEFICIALTOTHEPATIENTSPOST-OPERATIVELY:

Aim:Toassesswhichmethodofplacentaremovalhasmorebeneficialeffects,spontaneousremovalormanualremovalandadheretopracticesthatbenefitthepatient. Design:RETROSPECTIVECOHORTSTUDY Methodology: SampleSize:100 Inclusioncriteria: PostnatalpatientsProcedure:Thisstudyisaretrospectivecohortstudy.ThestudypopulationwillbepostnatalpatientswhodeliveredinChettinadHospital. After getting informed consent, the procedure will be explained thoroughly to the participantsand only the participants who are willing to take part in the study will be selected. Theparticipantswereobservedonanoutpatientbasisandthosewhowereadmittedinthepostnatalward. Parturients undergoing cesarean delivery were prospectively randomized to have theplacenta removed manually or spontaneously. Patients were excluded from participation if theyhad received intrapartum prophylactic antibiotics or had been determined to havechorioamnionitis. After delivery of the infant, women in the manual group had the placentaextracted by the primary surgeon, whereas women in the spontaneous group had the placentadelivered by gentle traction on the umbilical cord. All study subjects received perioperativeprophylactic antibiotics. Their pre operative and post operative reports were analyzed forHaemoglobin counts, their course of antibiotics and days of antibiotics taken post operativelywastakenintoconsideration,symptomssuchasDizziness,palpitations,headacheTirednessorweakness were asked to the patients and their complete blood counts report, urine routinereportswerecollectedtobecomparedpreandpostoperatively. Thisstudyisainvasivestudy. StudyDuration:2months(4/10/2023-04/12/2023)Results: A total of 100 women were enrolled in the investigation, with 48 assigned to the manual removalgroup and 52 allocated to have spontaneous removal. There were no statistically significantdifferencesinmeangestationalage,frequencyordurationofrupturedmembranes,frequencyordurationoflabor,ormeannumberofvaginalexaminationsbetweenthetwostudygroups. Postoperative infections occurred in 5 of 52 women in the spontaneous delivery groupcomparedwith12of48womeninwhichtheplacentawasmanuallyextracted.Subsetanalysisof patients delivered with ruptured membranes similarly demonstrated a statistically significantreduction in the incidence of postoperative infections with spontaneous placental removalcompared with manual extraction There was a similar trend toward a reduction in post deliveryinfectionsassociatedwithspontaneousplacentalremovalinwomenwithintactmembranes. Conclusion:Spontaneous delivery of the placenta after cesarean delivery is associated with a decrease intheincidenceofpostcesareaninfectionsandanemicsymptomscomparedtomanualremovaloftheplacenta.

The budget impact of procalcitonin-guided antibiotic stewardship compared to standard of care for patients with suspected sepsis admitted to the intensive care unit in Belgium.

In Belgium, antibiotic resistance leads to approximately 530 deaths with a €24 million financial burden annually. This study estimated the impact of procalcitonin-guided antibiotic stewardship programs to reduce antibiotic consumption versus standard of care in patients with suspected sepsis. A decision analytic tree modelled health and budget outcomes of procalcitonin-guided antibiotic stewardship programs for patients admitted to the intensive care unit (ICU). A literature search, a survey with local clinical experts, and national database searches were conducted to obtain model input parameters. The main outcomes were total budget impact per patient, reduction in number of antibiotic resistance cases, and cost per antibiotic day avoided. To evaluate the impact of parameter uncertainty on the source data, a deterministic sensitivity analysis was performed. A scenario analysis was conducted to investigate budget impact when including parameters for reduction in length of ICU stay and mechanical ventilation duration, in addition to base-case parameters. Based on model predictions, procalcitonin-guided antibiotic stewardship programs could reduce the number of antibiotic days by 66,868, resulting in €1.98 million savings towards antibiotic treatment in current clinical practice. Antibiotic resistance cases could decrease by 7.7% (6.1% vs 9.2%) in the procalcitonin-guided setting compared with standard of care. The base-case budget impact suggests an investment of €1.90 per patient. The sensitivity analysis showed uncertainty, as the main drivers can alter potential cost savings. The scenario analysis indicated a saving of €1,405 per patient, with a reduction of 1.5 days in the ICU (14.8 days vs 12.8 days), and a reduction of 22.7% (18.1-27.2%) in mechanical ventilation duration. The associated sensitivity analysis was shown to be robust in all parameters. Procalcitonin-guided antibiotic stewardship programs are associated with clinical benefits that positively influence antimicrobial resistance in Belgium. A small investment per patient to implement procalcitonin testing may lead to considerable cost savings.

Risk Factors for Post-Operative Multi-Drug-Resistant Organism Bacterial Infection in Patients With Stanford Acute Type A Aortic Dissection.

Background: To explore the risk factors for multi-drug-resistant organism (MDRO) infection in patients with Stanford acute type A aortic dissection (ATAAD). We conducted a retrospective cohort study using the data of post-operative patients with ATAAD in our hospital. Patients and Methods: This study included 82 post-operative patients with ATAAD in the past decade. They were divided into a MDRO group (n = 31) and a non-MDRO group (n = 51) according to whether they had acquired multi-drug-resistant (MDR) bacterial infection. Multivariable logistic regression was used to analyze the risk factors for MDR infections in patients with ATAAD. Results: The incidence of multi-drug-resistant bacterial infection was 37.80%. Seventeen factors, including hospital stay (p = 0.007), utilization of third-generation cephalosporins (p = 0.0068), antibiotic species of exposure (p = 0.0002), leukocyte-depleted red blood cell suspension dosage (p < 0.0001), fresh frozen plasma dosage (p < 0.0001), application of blood purification (p = 0.0493), and the total antibiotic days of exposure (p = 0.0001) diverged between the two groups (all p < 0.05). The logistic regression analysis revealed that the utilization of third-generation cephalosporins (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.01-5.33; p = 0.0478), antibiotic species of exposure (OR, 5.76; 95% CI, 1.45-22.83; p = 0.0128), leukocyte-depleted red blood cell suspension dosage (OR, 12.43; 95% CI, 2.71-57.07; p = 0.0012), and fresh frozen plasma dosage (OR, 5.05; 95% CI, 1.18-21.56; p = 0.0286) were independent variables for MDRO infections. Among the 23 drug-resistant bacteria detected, Acinetobacter baumannii was the main pathogen. Conclusions: Our study shows that the utilization of third-generation cephalosporins, antibiotic species of exposure, leukocyte-depleted red blood cell suspension dosage, and fresh frozen plasma dosage were independent risk factors for post-operative multi-drug-resistant infection in patients with ATAAD. Acinetobacter baumannii occupied the largest share of resistant bacteria that induce infection in post-operative patients with ATAAD.

A pharmacist-driven deprescribing protocol for negative urine and sexually transmitted infection cultures in the emergency department increases antibiotic-free days.

Emergency department (ED) pharmacists commonly perform positive culture follow-ups that result in optimized antibiotic prescribing. The purpose of this study was to evaluate the potential positive impact on the outcome of antibiotic-free days through an ED pharmacist-driven protocol to contact patients with negative urine cultures and sexually transmitted infection (STI) test results who were discharged with antibiotics. This was a single-center, prospective, observational, pre-post intervention study to determine antibiotic use in patients with negative urine cultures who were discharged from the Loyola Medical University Center ED with antibiotics prescribed. Patients were identified through daily positive culture reports. The primary outcome was days free of antibiotics, defined as the number of calendar days within 28 days after urine culture or STI test collection on which the patient did not receive any antibiotic treatments. One hundred ninety-two patients were screened. Sixty-three and twenty-six patients met the inclusion criteria in the pre- and postintervention groups, respectively. The study identified 163/465 (35.1%) antibiotic free days for the preintervention group, compared to 150.5/187 (80.5%) antibiotic-free days for the postintervention group. A majority of the patients did not have urinary tract infection as the chief complaint. The most common urinary and STI symptoms upon ED admission in the pre- and postintervention groups were dysuria (19.2% vs 28.1%) and unusual discharge (30.8% vs 28.6%), respectively. This study showed that a pharmacist-driven protocol increased the number of antibiotic-free days for patients prescribed empiric antibiotic therapy and discharged from the ED with subsequent negative urine cultures and STI results. We propose taking a novel approach in discontinuation of antibiotics by implementing an expansion of ED culture programs to include negative cultures that promote antimicrobial stewardship.

A quality improvement initiative standardizing the antibiotic treatment and feeding practices in patients with medical necrotizing enterocolitis.

Evaluate the impact of a multidisciplinary guideline standardizing antibiotic duration and enteral feeding practices following medical necrotizing enterocolitis (mNEC). For preterm infants with Bell Stage 2 A mNEC and negative blood culture, antibiotic treatment was standardized to 7 days. Trophic feeds of unfortified human milk began 72 h after resolution of pneumatosis. Feeds were advanced by 20 cc/kg/day starting on the last day of antibiotics. Primary outcomes were antibiotic days and days to full feeds, defined as 120 cc/kg/day of enteral nutrition. Secondary outcomes included central line days and length of stay (LOS). Antibiotic duration decreased 23%. Time to start trophic feeds and time to full feeds decreased 33 and 16% respectively. Central line use dropped (98 to 72% of infants) and central line days were reduced by 59%. Implementation of a mNEC QI package reduced antibiotic duration, time to full feeds, central line use and CL days.

Efficacy and Safety of Three Doses of Ceftriaxone and Metronidazole as Prophylactic Uses during Acute Non-Perforated Appendicitis Surgical Operation: A Randomized Control Trial

Background: This study compared the efficacy of prophylactic antibiotics with seven days of conventional antibiotics. Objective: This present study was carried out to evaluate the effectiveness of three doses of prophylaxis with ceftriaxone and metronidazole. Methodology: This parallel arm, randomized control trial was conducted among fifty patients, consisting of 25 cases and 25 controls, with acute appendicitis admitted at Dhaka Medical College Hospital, Popular Medical College Hospital, Dhaka, and Ad-din Barrister Rafique Ul-Haq Hospital, Dhaka, during the period of November 2021 to April 2022. This study was done to evaluate the efficacy of three doses of combined prophylactic antibiotics, ceftriaxone and metronidazole, in acute non-perforated appendicitis cases. The patients in the control group were treated with seven days of conventional antibiotic therapy to compare the efficacy with three doses of prophylactic antibiotics. Results: Among 9 wound infections (15%), 4 patients were in the control group (36.5%), and 5 (40.5%) were in the case group in the study group with combined surgical prophylaxis of ceftriaxone and metronidazole (P=0.001). One patient develops both a wound infection and an intra-abdominal abscess. The study also found that amount to patient (3.3%) with intra-abdominal abscess formation 01 (50%) in control group and 01(50.0%) in combined prophylaxis group (ceftriaxone and metronidazole) (P&gt;0.3). Conclusion: In conclusion no significant difference could be found between the patients who received combined three doses of ceftriaxone and metronidazole and the control groups with regard to age, sex, distribution of symptoms before admission, preoperative temperature, duration of surgery, hospital stay, and concomitant diseases both overall and within each of the three groups of appendiceal examination. Bangladesh Journal of Infectious Diseases, June 2023;10(1):11-15