Long Course Of Antibiotics Research Articles

Epidemiology and Duration of Therapy in Patients with Gram-negative Bloodstream Infections: Retrospective Analysis

Background: Longer courses of antibiotics can be associated with antimicrobial resistance and adverse effects. Randomized clinical trials support treating gram-negative bloodstream infections (GN-BSI) for a shorter duration with a consensus that a seven-day course of antibiotics is appropriate for uncomplicated GN-BSI. Prior to the implementation of a GN-BSI treatment guideline at our institution, we aimed to evaluate the characteristics of patients with GN-BSI and the duration of antibiotic therapy (DOT). Method: We retrospectively reviewed adult inpatients who had a blood culture with at least 1 gram-negative organism within 6 months (November 2022 to April 2023). Patients were excluded if they had a concomitant gram-positive bloodstream infection or if they were transitioned to comfort-focused care within 48 hours of their first positive blood culture. Complicated GN-BSI was defined as exhibiting any of the following: involvement of bone, joint, endovascular system, or foreign body, an inability to achieve source control, immunocompromised status, or failure to demonstrate clinical improvement or culture clearance within 72 hours. The primary outcome of this study was the mean DOT in patients with GN-BSI. Result: 100 patients met the inclusion criteria. Escherichia coli, identified in 54 cases, emerged as the most frequent organism. Urine (41) was the predominant source of bacteremia. Cefepime (48) was the most common empiric agent used. Of the 91 patients with available ceftriaxone susceptibility results, 84% had a susceptible organism. Amongst the 51 patients classified as having a complicated GN-BSI, the leading reason was immunosuppression. Table 1 presents a comparative analysis of complicated vs. uncomplicated GN-BSI. The average DOT for complicated GN-BSI was longer than the uncomplicated infections (20 vs. 11 days, P < 0 .005). Additionally, fewer patients transitioned to oral therapy in the complicated group (33% vs. 67%, P < 0 .005). Conclusion: At our institution, patients with uncomplicated GN-BSI have a shorter DOT and are more likely to transition to oral therapy than those with complicated GN-BSI. However, the mean DOT for uncomplicated infections remained longer than seven days and a large number of uncomplicated GN-BSI patients did not transition to oral therapy, indicating room for improvement in local practice through antimicrobial stewardship initiatives.

The Use of Long-term Antibiotics for Suppression of Bacterial Infections.

Suppressive antibiotic therapy is prescribed when a patient has an infection that is presumed to be incurable by a defined course of therapy or source control. The cohort receiving suppressive antibiotic therapy is typically highly comorbid and the infections often involve retained prosthetic material. In part due to a lack of clear guidelines regarding the use of suppressive antibiotics, and in part due to the complex nature of the infections in question, patients are often prescribed suppressive antibiotics for extremely long, if not indefinite, courses. The risks of prolonged antibiotic exposure in this context are not fully characterized, but they include adverse drug effects ranging from mild to severe, the development of antibiotic-resistant organisms, and perturbations of the gastrointestinal microbiome. In this narrative review we present the available evidence for the use of suppressive antibiotic therapy in 4 common indications, examine the gaps in the current literature, and explore the known and potential risks of this therapy. We also make suggestions for improving the quality of evidence in future studies, particularly by highlighting the need for a standardized term to describe the use of long courses of antibiotics to suppress hard-to-treat infections.

High-Risk Patients Undergoing Holmium Laser Enucleation of the Prostate Have Fewer Infections with a Longer Course of Preoperative Antibiotics.

Introduction: There are minimal data to guide antibiotic management of patients undergoing holmium laser enucleation of the prostate (HoLEP) for benign prostatic hyperplasia. Specifically, management of high-risk patients who are catheter dependent or have positive preoperative urine cultures varies widely. We aimed to evaluate the effect of preoperative antibiotic duration on infectious complications in high-risk patients undergoing HoLEP. Methods: A multi-institutional retrospective review of patients undergoing HoLEP between 2018 and 2023 at five institutions was performed. Patients were defined as high risk if they were catheter-dependent (indwelling urethral catheter, self-catheterization, or suprapubic tube) or had a positive preoperative urine culture. These patients were categorized into long course (>3 days) or short course (≤3 days) of preoperative antibiotics. The primary outcome was 30-day infectious complications defined as a positive urine culture with symptoms. A t-test or Wilcoxon rank-sum test was used for continuous variables and Fisher's exact test was used for categorical variables. Logistic regression analysis was conducted to identify associations with infectious complications. Results: Our cohort included 407 patients, of which 146 (36%) and 261 (64%) were categorized as short course and long course of preoperative antibiotics, respectively. Median preoperative antibiotic duration was 1 day (interquartile range [IQR]: 0, 3 days) and 7 days (IQR: 5, 7 days) in the short and long cohorts, respectively. Thirty-day postoperative infectious complications occurred in 11 (7.6%) patients who received a short course of antibiotics and 5 (1.9%) patients who received a long course of antibiotics (odds ratio 0.24, 95% confidence interval 0.07-0.67; p = 0.009). Variables such as age, positive urine culture, and postoperative antibiotic duration were not significantly associated with postoperative infection after propensity score weighting. Conclusion: In high-risk patients undergoing HoLEP, infectious complications were significantly lower with a long course vs short course of antibiotics. Further prospective trials are needed to identify optimal preoperative antibiotic regimens.

Prevalence of chronic rhinosinusitis without/with nasal polyps according to severity in Spain.

The worldwide prevalence range of chronic rhinosinusitis (CRS) is 5-12%; from this, 20 % have nasal polyps. Due to the little epidemiological data about CRS in the Spanish population, this study analyses the prevalence and severity of CRS with (CRSwNP) or without (CRSsNP) nasal polyps, and their connection with other coexisting type 2 inflammatory diseases in Spain. This is a retrospective, large-scale, nationwide, epidemiological study based on the electronic medical records from the BIG-PAC® database. Patients diagnosed of CRSsNP and CRSwNP were identified using specific disease codes. The severe form of the disease was defined as patients who received at least a long course of antibiotics in CRSsNP or ≥2 short courses of systemic corticosteroids in CRSwNP in ≤12 months during the last 2 years, and/or had previous sinus surgery. Physician diagnosed prevalence, sociodemographic and clinical characteristics, and disease severity were assessed. Out of a cohort of 1,012,257 patients (≤18 years old), 42,863 and 7,550 patients with diagnosed CRSsNP and CRSwNP, respectively, were analysed. The overall prevalence of diagnosed CRS was 5.1%, being 4.3% and 0.8% for CRSsNP and CRSwNP, respectively. Patients with CRSwNP and severe forms of the disease were older and had higher levels of type 2 inflammatory biomarkers than CRSsNP patients and non-severe disease. Although CRSsNP was more prevalent than CRSwNP, the severe forms of CRS were more frequent in patients with CRSwNP. In addition, CRSwNP patients had a higher incidence of coexisting type 2 inflammatory diseases.

Post-operative antibiotic prophylaxis in spine surgery patients with thoracolumbar drains: A meta analysis

Closed-suction drains are commonly placed after thoracolumbar surgery to reduce the risk of post-operative hematoma and neurologic deterioration, and may stay in place for a longer period of time if output remains high. Prolonged maintenance of surgical site drains, however, is associated with an increased risk of surgical site infection (SSI). The present study aims to examine the literature regarding extended duration (≥24h) prophylactic antibiotic use in patients undergoing posterior thoracolumbar surgery with closed-suction drainage. This systematic review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Relevant studies reporting the use of 24-h post-operative antibiotics compared with extended duration post-operative antibiotics in patients undergoing posterior thoracolumbar surgery with closed-suction drainage were identified from a PubMed database query. Six studies were included for statistical analysis, encompassing 1003 patients that received 24h of post-operative antibiotics and 984 patients that received ≥24h of post-operative antibiotics. The SSI rate was 5.16% for the shorter duration group (24h) and 4.44% (p=0.7865) for the longer duration group (≥24h). There is no significant difference in rates of SSI in patients receiving 24h of post-operative antibiotics compared with patients receiving ≥24h of post-operative antibiotics. Shorter durations of post-operative antibiotics in patients with thoracolumbar drains have similar outcomes compared to patients receiving longer courses of antibiotics. Shorter durations of antibiotics could potentially help lead to lower overall cost and length of stay for these patients.

Evaluation of Short Versus Long Courses of Antibiotics in Critically Ill Patients With Gram-Negative Bloodstream Infections.

Short courses of antibiotics (7-10 days) are effective for uncomplicated gram-negative bloodstream infections (GN-BSI). However, prior studies have been limited to small cohorts of critically ill patients. The objective of this study was to evaluate the safety and efficacy of short courses of therapy compared with longer courses in patients admitted to the intensive care unit (ICU) with GN-BSI. Propensity-matched, retrospective cohort study of critically ill patients with GN-BSI. The primary outcome was a composite of 30-day mortality or 60-day relapse. Secondary endpoints were components of the composite, 30-day relapse, cure with or without adverse drug events (ADE), and ADEs. Regression analysis was performed to identify factors predictive of the composite outcome. 225 patients were included in the propensity analysis, 145 in the long cohort and 80 in the short cohort. The primary outcome occurred in 3.8% of patients in the short group and 9.0% of patients in the long group (P = 0.24). There was no difference in 30-day mortality (3.8% vs 5.5%, P = 0.79), 60-day relapse (0% vs 3.4%, P = 0.23), or 30-day readmission (20% vs 22.8%, P = 0.76). ADEs were more common in the long group (47.2% vs 34.1%, OR 1.7, 95% CI 1.04-2.9), primarily attributable to diarrhea. In critically ill patients with GN-BSI, there were no efficacy outcome differences in patients treated with a short course of antibiotics compared with longer. However, patients in the short group were less likely to experience ADE. These findings suggest that short courses of antibiotics are effective for GN-BSI in critically ill patients.

Hidradenitis suppurativa in children and young adults: a retrospective cross-sectional observational study in the United Kingdom.

Hidradenitis suppurativa (HS) in children and young adults (CYA) (<18 years) is uncommon. No previous observational studies have been carried out in a UK CYA HS population. This study was based on retrospective case note reviews of CYA HS patients attending tertiary-level care in the CYA HS service in a UK hospital. Patients <18 years old with a known diagnosis of HS were screened for inclusion. Exclusion criteria were those with less than one follow-up appointment. Twenty-eight CYA HS patients were identified, with an M:F ratio of 1:8.3. Mean BMI was 25.2 (SD: 7.6). 17 (61%) of cases had a relevant family history. Long-term antibiotic monotherapy was the most common treatment initiated. Lymecycline was the most commonly prescribed antibiotic, accounting for 23 (56%) of the 41 courses prescribed. Additional treatments initiated included dual therapy with rifampicin and clindamycin, isotretinoin, and adalimumab, which were more commonly prescribed in patients with Hurley Stage II or III. This group had a female predominance with an apparent strong genetic predisposition which is seen in other HS CYA cross-sectional research. Treatment was varied in this cohort, however long courses of antibiotics, including combined therapy with rifampicin and clindamycin, were the mainstay of treatment, similar to management in the adult population. This study therefore adds to the limited information on the demographics and management of the HS CYA population.

Clinical Characteristics and Treatment Outcomes of Pediatric Bacterial Skin and Soft Tissue Infections in Central Vietnam: A Prospective Study.

Objective. This study examined bacterial skin and soft tissue infections (SSTIs) in pediatric patients at a hospital in Vietnam. Methods. An April 2022-June 2023 prospective obsevational study at a Tertiary Paediatric Centre in Vietnam. Results. From We analyzed 87 cases and found that the greatest occurrence rates were reported during the summer season. Common symptoms were fever, edema, and lower leg involvement. Curiously, although blood cultures seldom verified the offender, Staphylococcus aureus was the most common cause. Additionally, the study found that children with infections including pus were administered a more extended course of antibiotics. Approximately one-third of the patients underwent surgical procedures, and most of them were administered intravenous antibiotics. Fortunately, all the youngsters made a full recovery. Conclusions. In summary, the results indicate that children with purulent SSTIs, primarily attributed to Staphylococcus aureus, may need longer courses of antibiotics. Intravenous antibiotic administration emerged as the predominant therapeutic modality.

Metabolic modeling predicts unique drug targets in Borrelia burgdorferi.

Lyme disease is often treated using long courses of antibiotics, which can cause side effects for patients and risks the evolution of antimicrobial resistance. Narrow-spectrum antimicrobials would reduce these risks, but their development has been slow because the Lyme disease bacterium, Borrelia burgdorferi, is difficult to work with in the laboratory. To accelerate the drug discovery pipeline, we developed a computational model of B. burgdorferi's metabolism and used it to predict essential enzymatic reactions whose inhibition prevented growth in silico. These predictions were validated using small-molecule enzyme inhibitors, several of which were shown to have specific activity against B. burgdorferi. Although the specific compounds used are not suitable for clinical use, we aim to use them as lead compounds to develop optimized drugs targeting the pathways discovered here.

DS27 Establishing clinician and patient perspectives on a proposed trial investigating antibiotics in skin surgery

Abstract Surgical site infection (SSI) following excision of ulcerated skin cancers is a well-recognized complication; however, the exact risk is unknown and there is no consensus on antibiotic prescribing in this setting. The EXCISE trial (EXamining antibiotics for ulCerated skIn cancer Surgical Excision) aims to address this evidence gap. An online survey was distributed to the UK Dermatology Clinical Trials Network (UKDCTN), British Society for Dermatological Surgery and plastic surgery, ear, nose and throat (ENT) and maxillofacial surgery networks (December 2022). The survey aimed to establish clinicians’ views about the proposed EXCISE trial. A focus group with patient representatives with lived experience of skin cancer surgery was also conducted (n = 5). Ninety questionnaire responses were received: six plastic surgeons (7%), 19 oral and maxillofacial surgeons (21%), four ENT surgeons (4%) and 61 dermatologists (68%). Sixty-five per cent of responders were consultants, and 34% were registrars. Seventy-one (79%) were willing to recruit to the EXCISE trial. Forty-eight (53%) agreed to randomize patients to 0 (no antibiotics), 1, 2, 3, 5 or 7 days of postoperative flucloxacillin. Thirty-seven (41%) agreed a 6–10% absolute increase in risk of SSI would justify a shorter course of antibiotics (1–3 days) with fewer side-effects. Thirty-three (37%) felt a 0–5% absolute risk increase would be acceptable, 17 (19%) felt an absolute risk increase of 11% or greater was acceptable, and three (3%) did not respond. Eighty-one (90%) agreed that if the EXCISE trial demonstrated a reduction in SSI, they would prescribe antibiotics, 61 (68%) would prescribe longer courses (5–7 days) and 17 (19%) would prescribe shorter courses (1–3 days). Patients reported a preference for shorter antibiotic courses (1–3 days) vs. longer (5–7 days) if there were fewer side-effects and no increased risk of infection. All patients agreed, in principle, to randomization to the proposed groups and highlighted the need to recruit from diverse socioeconomic backgrounds. They also suggested highlighting zero days of postoperative antibiotics often reflects usual practice to encourage participation. All participants agreed with the proposed 10% noninferiority margin. In summary, our data demonstrate acceptability of the proposed EXCISE trial among both clinicians and patients. An absolute noninferiority margin of 10% between SSIs occurring in the context of longer courses of antibiotics vs. shorter courses of antibiotics is acceptable to patients when associated with fewer side-effects. Clinicians showed mixed responses, suggesting that further work is required to explore the barriers and facilitators to prescribing and for future implementation. Acknowledgments: The study was developed with support from the UK Dermatology Clinical Trials Network (UK DCTN). The UKDCTN is grateful to the British Association of Dermatologists and the University of Nottingham for financial support of the network.

Spondylodiscitis following ingestion of button battery in an infant-a case-based update.

Button battery ingestion in infants is an increasingly common surgical emergency which can lead to oesophageal perforation, mediastinitis, trachea-oesophageal fistulation, airway compromise and death. One exceedingly rare complication of battery ingestion is discitis and osteomyelitis in the cervical and upper thoracic spine. Diagnosis is normally delayed due to the non-specific presentation, delayed imaging findings and the initial clinical focus on dealing with the immediate, and potentially life-threatening, complications. We describe a case of a 1-year-old girl who presented with haematemesis and an oesophageal injury, secondary to button battery ingestion. Sagittal reconstruction of the CT chest demonstrated a suspicious area of vertebral erosion in the cervicothoracic spine which prompted a further evaluation with MRI demonstrating spondylodiscitis of C7-T2 with vertebral erosion and collapse. The child was successfully treated with long course of antibiotics. We wish to highlight the importance of clinical and radiological spinal assessment in children with button battery ingestion to avoid delayed diagnosis and complications of spinal osteomyelitis.

Duration of antibiotic therapy among paediatricians: A national survey of current clinical practice in Spain

Appropriate duration of antibiotic treatment is a key principle to reduce the emergence of bacterial resistance and antibiotic harm. The aim of this study was to document current clinical practice among Spanish paediatricians in terms of the duration of antibiotic therapy in both inpatient and outpatient settings, mapping the difference between practice and guidelines, and thus identifying opportunities to improve practice. A national exploratory work survey was distributed in 2020 as a questionnaire about seven main infectious syndromes in children: genitourinary; skin and soft tissue; osteoarticular; ear, nose and throat; pneumonia; central nervous system; and bacteraemia. The answers were contrasted with current recommendations regarding the duration of antibiotic therapy. Demographic analysis was also performed. The survey was completed by 992 paediatricians in Spain, representing 9.5% of paediatricians working in the Spanish national health system. Hospital care clinicians accounted for 42.7% (6662/15590) of responses. The antibiotic duration used in practice was longer than recommended in 40.8% (6359/15590) of responses, and shorter than recommended in 16% (1705/10654) of responses. Only 25% (249/992) and 23% (229/992) of respondents indicated that they would prescribe antibiotics for the recommended treatment duration for lower urinary tract infection and community-acquired pneumonia (AI evidence). Among severe hospital-managed infections, a tendency towards longer courses of antibiotics was found for non-complicated meningococcal infections and non-complicated pneumococcal, Gram-negative and S. aureus bacteraemia. A noteworthy tendency towards prescribing antibiotics for longer than recommended among paediatricians was evidenced in this nationwide study, highlighting a wide range of opportunities for potential improvement.

Re-examining advice to complete antibiotic courses: a qualitative study with clinicians and patients.

Antibiotic treatment duration may be longer than sometimes needed. Stopping antibiotics early, rather than completing pre-set antibiotic courses, may help reduce unnecessary exposure to antibiotics and antimicrobial resistance (AMR). To identify clinicians' and patients' views on stopping antibiotics when better (SAWB) for urinary tract infections (UTIs), and to explore comparisons with other acute infections. An exploratory qualitative study with general practice clinicians and patients in England. Primary care clinicians and patients who had recent UTI experience were recruited in England. Remote one-to-one interviews with clinicians and patients, and one focus group with patients, were conducted. Data were audiorecorded, transcribed, and analysed thematically. Eleven clinicians (seven GPs) and 19 patients (14 with experience of recurrent and/or chronic UTIs) were included. All participants considered SAWB unfamiliar and contradictory to well-known advice to complete antibiotic courses, but were interested in the evidence for risks and benefits of SAWB. Clinicians were amenable if evidence and guidelines supported it, whereas patients were more averse because of concerns about the risk of UTI recurrence and/or complications and AMR. Participants viewed SAWB as potentially more appropriate for longer antibiotic courses and other infections (with longer courses and lower risk of recurrence and/or complications). Participants stressed the need for unambiguous advice and SAWB as part of shared decision making and personalised advice. Patients were less accepting of SAWB, whereas clinicians were more amenable to it. Patients and clinicians require good evidence that this novel approach to self-determining antibiotic duration is safe and beneficial. If evidence based, SAWB should be offered with an explanation of why the advice differs from the 'complete the course' instruction, and a clear indication of when exactly to stop antibiotics should be given.

Antibiotic Prescribing in Outpatient Settings: Rural Patients Are More Likely to Receive Fluoroquinolones and Longer Antibiotic Courses.

Suboptimal antibiotic prescribing may be more common in patients living in rural versus urban areas due to various factors such as decreased access to care and diagnostic testing equipment. Prior work demonstrated a rural health disparity of overprescribing antibiotics and longer durations of antibiotic therapy in the United States; however, large-scale evaluations are limited. We evaluated the association of rural residence with suboptimal outpatient antibiotic use in the national Veterans Affairs (VA) system. Outpatient antibiotic dispensing was assessed for the veterans diagnosed with an upper respiratory tract infection (URI), pneumonia (PNA), urinary tract infection (UTI), or skin and soft tissue infection (SSTI) in 2010-2020. Rural-urban status was determined using rural-urban commuting area codes. Suboptimal antibiotic use was defined as (1) outpatient fluoroquinolone dispensing and (2) longer antibiotic courses (>ten days). Geographic variation in suboptimal antibiotic use was mapped. Time trends in suboptimal antibiotic use were assessed with Joinpoint regression. While controlling for confounding, the association of rurality and suboptimal antibiotic use was assessed with generalized linear mixed models with a binary distribution and logit link, accounting for clustering by region and year. Of the 1,405,642 veterans diagnosed with a URI, PNA, UTI, or SSTI and dispensed an outpatient antibiotic, 22.8% were rural-residing. In 2010-2020, in the rural- and urban-residing veterans, the proportion of dispensed fluoroquinolones declined by 9.9% and 10.6% per year, respectively. The rural-residing veterans were more likely to be prescribed fluoroquinolones (19.0% vs. 17.5%; adjusted odds ratio (aOR), 1.03; 95% confidence interval (CI), 1.02-1.04) and longer antibiotic courses (53.8% vs. 48.5%; aOR, 1.19, 95% CI, 1.18-1.20) than the urban-residing veterans. Among a large national cohort of veterans diagnosed with URIs, PNA, UTIs, and SSTIs, fluoroquinolone use and longer antibiotic courses were disproportionally more common among rural- as compared to urban-residing veterans. Outpatient antibiotic prescribing must be improved, particularly for rural-residing patients. There are many possible solutions, of which antibiotic stewardship interventions are but one.

Is There Any Benefit to the Use of Antibiotics with Indwelling Catheters after Urologic Surgery in Adults.

Antibiotic stewardship in urologic reconstruction is critically important, as many patients will require indwelling catheters for days to weeks following surgery and thus are at risk of both developing catheter-associated urinary tract infections (CAUTI) as well as multi-drug resistant (MDR) uropathogens. Accordingly, limiting antibiotic use, when safe, should help reduce antibiotic resistance and the prevalence of MDR organisms. However, there is significant heterogeneity in how antibiotics are prescribed to patients who need indwelling urethral catheters post-operatively. We performed a literature review to determine if there are benefits in the use of antibiotics for various clinical scenarios that require post-operative indwelling catheters for greater than 24 h. In general, for patients undergoing prostatectomy, transurethral resection of the prostate, and/or urethroplasty, antibiotic administration may be limited without increased risk of CAUTI. However, more work is needed to identify optimal antibiotic regimens for these and alternative urologic procedures, whether certain sub-populations benefit from longer courses of antibiotics, and effective non-antibiotic or non-systemic therapies.

Antibiotic treatment duration for culture-negative sepsis in the pediatric intensive care unit.

Sepsis remains a leading cause of morbidity and mortality in children. There is very limited guidance for sepsis treatment when cultures remain negative. This study sought to determine the effectiveness of short versus long course of antibiotics when treating culture-negative sepsis and assess for subsequent multidrug-resistant organism (MDRO) acquisition. Retrospective cohort study. Quaternary academic children's hospital. Pediatric intensive care unit (ICU) patients with culture-negative sepsis receiving a minimum of 72 hours of antibiotics. Patients found to have culture-negative sepsis from January 2017 to May 2020 were divided into two groups: short and long course of antibiotics. Various demographic and laboratory results were collected for each subject as available. Primary outcomes included mortality and lengths of stay. The secondary outcome was subsequent acquisition of a new MDRO. Eighty-six patients were treated for culture-negative sepsis with 43 patients in both the short- (< or = 7 days) and long-course (>7 days) treatment cohorts. Patients who received a short course of antibiotics had a lower overall mortality than those who received a long course (9.3% vs 25.6% p = 0.047), but there was no difference in 30-day mortality (p > 0.99). Patients in the short-course group had a shorter hospital length of stay (22 vs 30 days p = 0.018). New MDROs were found in 10% of all patients. Treatment of culture-negative sepsis with short-course antibiotics was not associated with worse outcomes in ICU patients. These findings warrant further investigation with a larger, prospective, multi-center study.

1242: PEDIATRIC SEPSIS HAS HIGH MORTALITY REGARDLESS OF PATHOGEN IDENTIFICATION

Introduction: Sepsis remains a major cause of morbidity and mortality in critically ill children worldwide. Culture-negative sepsis (CNS) is diagnosed when a patient meets the criteria for sepsis with no causative pathogen identified. The etiology of CNS may be an uncultivable pathogen, treatment with antimicrobials before a culture was drawn, or a non-infectious cause. For adults, CNS is estimated to comprise up to 50% of all ICU admissions for sepsis, but the characteristics of the pediatric population with CNS are poorly understood. Methods: This is a retrospective cohort study of 3 pediatric ICUs within an urban, tertiary children’s hospital. All patients who received piperacillin-tazobactam, the institution’s standard initial broad-spectrum agent, were screened for study inclusion. Patients ≤18 years old who were hospitalized between March 2020 and February 2021 and met the criteria for sepsis defined in the 2020 Pediatric Surviving Sepsis Guidelines were included in the study. Results: Of the 302 patients screened, 61 met the criteria for sepsis. Thirty-two patients (52.5%) had culture-positive sepsis (CPS) and 29 patients (47.5%) had CNS. The median age for CPS was 5 years (interquartile range [IQR] 1-15y) and 3 years (IQR 0.5-15y) for CNS. Both groups had similar numbers of medically complex patients with >3 comorbidities (68.8% for CPS vs 70% for CNS, p=0.98). There was no statistically significant difference in mortality (28.1% CPS vs 17.2% CNS, p=0.32), need for mechanical ventilation (62.5% vs 58.6%, p=0.19), need for vasoactive medication (62.5% vs 55.2%, p=0.41), or median ICU and hospital length of stay (47 vs 27d, p=0.11; 53 vs. 27d, p=0.07) between groups. CPS patients were treated with longer courses of antibiotics (median 10 vs 7d for CNS p=0.03). Conclusions: When compared to CPS, outcomes for patients with CNS were similar though overall rates of mortality in both groups were high compared to previous reports (4-15%). Patients with CNS comprised a considerable proportion of the total number of patients with sepsis. A median ICU length of stay of 27 days for CNS patients represents significant resource utilization for these individual children. Given these findings, further studies are warranted to better understand this population and determine optimal treatment strategies.

Short-Course vs Long-Course Antibiotic Therapy for Children With Nonsevere Community-Acquired Pneumonia

Short-course antibiotic therapy could enhance adherence and reduce adverse drug effects and costs. However, based on sparse evidence, most guidelines recommend a longer course of antibiotics for nonsevere childhood community-acquired pneumonia (CAP). To determine whether a shorter course of antibiotics was noninferior to a longer course for childhood nonsevere CAP. MEDLINE, Embase, Web of Science, the Cochrane Library, and 3 Chinese databases from inception to March 31, 2022, as well as clinical trial registries and Google.com. Randomized clinical trials comparing a shorter- vs longer-course therapy using the same oral antibiotic for children with nonsevere CAP were included. Random-effects models were used to pool the data, which were analyzed from April 15, 2022, to May 15, 2022. Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to rate the quality of the evidence. Treatment failure, defined by persistence of pneumonia or the new appearance of any general danger signs of CAP (eg, lethargy, unconsciousness, seizures, or inability to drink), elevated temperature (>38 °C) after completion of treatment, change of antibiotic, hospitalization, death, missing more than 3 study drug doses, loss to follow-up, or withdrawal of informed consent. Nine randomized clinical trials including 11 143 participants were included in this meta-analysis. A total of 98% of the participants were aged 2 to 59 months, and 58% were male. Eight studies with 10 662 patients reported treatment failure. Treatment failure occurred in 12.8% vs 12.6% of participants randomized to a shorter vs a longer course of antibiotics. High-quality evidence showed that a shorter course of oral antibiotic was noninferior to a longer course with respect to treatment failure for children with nonsevere CAP (risk ratio, 1.01; 95% CI, 0.92-1.11; risk difference, 0.00; 95% CI, -0.01 to 0.01; I2 = 0%). A 3-day course of antibiotic treatment was noninferior to a 5-day course for the outcome of treatment failure (risk ratio, 1.01; 95% CI, 0.91-1.12; I2 = 0%), and a 5-day course was noninferior to a 10-day course (risk ratio, 0.87; 95% CI, 0.50-1.53; I2 = 0%). A shorter course of antibiotics was associated with fewer reports of gastroenteritis (risk ratio, 0.79; 95% CI, 0.66-0.95) and lower caregiver absenteeism (incident rate ratio, 0.74; 95% CI, 0.65-0.84). Results of this meta-analysis suggest that a shorter course of antibiotics was noninferior to a longer course in children aged 2 to 59 months with nonsevere CAP. Clinicians should consider prescribing a shorter course of antibiotics for the management of pediatric nonsevere CAP.

Characteristics of patients with xanthogranulomatous pyelonephritis undergoing nephrectomy: Identifying ways to optimise outcomes

Objective: This study is conducted to investigate characteristics of patients with xanthogranulomatous pyelonephritis (XGP) who undergo nephrectomy and to identify ways to optimise outcomes for these patients. Materials and methods: 1587 patients were queried from our institutional electronic medical records. 12 patients who underwent nephrectomy with preoperative diagnoses of XGP in the operative note were identified. Associations were analysed with Kendall’s τb. p &lt; 0.05 was statistically significant. Results: All patients were hemodynamically stable on day of surgery. Two patients died on postoperative days 1 and 3 from septic shock. Both had surgery during inpatient admission rather than electively, received relatively short duration of preoperative antibiotics (8 and 10 days), and both were on hemodialysis preoperatively. There was possible association between decreased glomerular filtration rate (τb = −0.550, p = 0.032) and death postoperatively. Among patients who lived, there was no significant association between duration of antibiotic therapy after intervention and duration of postoperative hospitalisation. Conclusion: These findings could suggest a possible association between declining renal function and mortality in our case series; and performing nephrectomy electively after a longer course of antibiotics may be associated with improved outcomes compared to nephrectomy performed during hospitalisation with a shorter course of antibiotics. Level of evidence: Level 4

An audit of acute respiratory antibiotic prescribing in COPD patients during the COVID-19 pandemic

IntroductionCoronavirus-2 is the virus responsible for the COVID-19 pandemic. People with certain risk factors, such as having chronic obstructive pulmonary disease (COPD) may be more likely to develop complications. Research has identified that ~7% of patients with COVID-19 have a bacterial infection, however antibiotic prescribing rates have been found to vary from 38% to 72% (1,2). Primary care is estimated to make up 75% of antibiotic prescribing and was therefore a key target to evaluate whether antimicrobial stewardship principles were being followed during the COVID-19 pandemic.AimTo audit the adherence of antibiotic prescribing in people with COPD during the COVID-19 pandemic across a primary care network (PCN) in England against national and local guidelines.MethodsThe management of patients with COPD should follow NICE Guideline (NG) 114, NG168 and the local formulary. Three audit standards were created: 1) 100% of COPD patients should not be started on prophylactic antibiotics to reduce risk from COVID-19; 2) 100% of COPD patients should not be prescribed antibiotics for COVID-19 symptoms; 3) 90% of antibiotic prescription regimens should adhere to local and national guidelines. Prescribing data was collected from 12 practices linked to the PCN. Data of patients who had COPD, were prescribed an antibiotic, and had an indication for the antibiotic between 01/03/20 and the 30/06/20 were extracted and transferred into an anonymised spreadsheet. A total of 1088 data points were extracted. Random stratified sampling provided 300 data points for analysis, ensuring each GP surgery was represented proportionally; the required sample size to determine significance was 291. For each practice, the total number of antibiotics prescribed to COPD patients between March-June 2019 and March-June 2020 was extracted. Descriptive statistics were used to determine antibiotic prescribing adherence and overall rates of prescribing. Inferential statistics were used to compare rates of prescribing pre-vs-during the pandemic.ResultsAntibiotics were not prescribed for any patient for prophylaxis against COVID-19 (100% adherence to criteria 1). Two patients were prescribed antibiotics for ‘suspected disease caused by COVID-19’ (99.4% adherence to criteria 2). In only 28.7% of cases, the antibiotic was prescribed in line with the national and local guidelines (criteria 3). In most cases, treatment duration was the main reason for poor adherence, with longer courses of antibiotics being prescribed (7 rather than 5 days). Prescribing rates did not change significantly in 2020 compared to 2019 (1134 antibiotic prescriptions vs 1029 antibiotic prescriptions; p>0.05).ConclusionThe audit was successful in determining that the COVID-19 pandemic did not significantly affect antibiotic prescribing rates across the PCN for people with COPD. Adherence to NICE and local guidelines was low, specifically concerning the duration of antibiotic treatment. This highlights an area for improvement; to ensure healthcare professionals across the PCN prescribe in-line with antimicrobial stewardship principles. Extracted data was limited to antibiotic prescribing and could have been expanded to include steroids to provide a fuller audit of prescribing in COPD exacerbations. A re-audit may be beneficial since the publication of NG191.References(1) Lansbury L, Lim B, Baskaran V, Lim WS. Co-infections in people with COVID-19: a systematic review and meta-analysis. J Infect. 2020 Aug;81(2):266-275.(2) Seaton RA, Gibbons CL, Cooper L, Malcolm W, McKinney R, Dundas S, Griffith D, Jeffreys D, Hamilton K, Choo-Kang B, Brittain S, Guthrie D, Sneddon J. Survey of antibiotic and antifungal prescribing in patients with suspected and confirmed COVID-19 in Scottish hospitals. J Infect. 2020 Dec;81(6):952-960.