Antibiotics For Community-acquired Pneumonia Research Articles

Optimizing discharge antimicrobial therapy: Evaluation of a transitions of care process and electronic scoring system for patients with community-acquired pneumonia or chronic obstructive pulmonary disease.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Prescribing excess antibiotic duration at hospital discharge is common. A pharmacist-led Antimicrobial Stewardship Program Transition of Care (ASP TOC) intervention was associated with improved discharge prescribing. To improve the sustainability of this service, an electronic scoring system (ESS), which included the ASP TOC electronic variable, was implemented in the electronic medical record to prioritize pharmacist workload. The purpose of this study was to evaluate the implementation of the ASP TOC variable in the ESS in patients with community-acquired pneumonia (CAP) or chronic obstructive pulmonary disease (COPD). This institutional review board-approved, retrospective quasi-experiment included patients discharged on oral antibiotics for CAP or COPD exacerbation (lower respiratory tract infection) from November 1, 2021, to March 1, 2022 (the preintervention period) and November 1, 2022, to March 1, 2023 (the postintervention period). The primary endpoint was optimized discharge antimicrobial regimen. A sample of at least 194 patients was required to achieve 80% power to detect a 20% difference in the frequency of optimized therapy. Multivariable logistic regression was used to identify factors associated with optimized regimens. Similar baseline characteristics were observed in both study groups (n = 100 for both groups). The frequency of optimized discharge regimens improved from 69% to 82% (P = 0.033). The percentage of ASP TOC interventions documented as completed by a pharmacist increased from 4% to 25% (P < 0.001). ASP TOC intervention, female gender, and COPD were independently associated with an optimized discharge regimen (adjusted odds ratios, 6.57, 1.61, and 3.89, respectively; 95% CI, 1.51-28.63, 0.81-3.17, and 1.85-8.20, respectively). After the launch of the ASP TOC variable, there was an increase in optimized discharge regimens and ASP TOC interventions completed. Pharmacists' use of the ASP TOC variable through an ESS can aid in improving discharge prescribing.

Identifying the Best Initial Oral Antibiotics for Adults with Community-Acquired Pneumonia: A Network Meta-Analysis.

The objective of this network meta-analysis was to compare rates of clinical response and mortality for empiric oral antibiotic regimens in adults with mild-moderate community-acquired pneumonia (CAP). We searched PubMed, Cochrane, and the reference lists of systematic reviews and clinical guidelines. We included randomized trials of adults with radiologically confirmed mild to moderate CAP initially treated orally and reporting clinical cure or mortality. Abstracts and studies were reviewed in parallel for inclusion in the analysis and for data abstraction. We performed separate analyses by antibiotic medications and antibiotic classes and present the results through network diagrams and forest plots sorted by p-scores. We assessed the quality of each study using the Cochrane Risk of Bias framework, as well as global and local inconsistency. We identified 24 studies with 9361 patients: six at low risk of bias, six at unclear risk, and 12 at high risk. Nemonoxacin, levofloxacin, and telithromycin were most likely to achieve clinical response (p-score 0.79, 0.71, and 0.69 respectively), while penicillin and amoxicillin were least likely to achieve clinical response. Levofloxacin, nemonoxacin, azithromycin, and amoxicillin-clavulanate were most likely to be associated with lower mortality (p-score 0.85, 0.75, 0.74, and 0.68 respectively). By antibiotic class, quinolones and macrolides were most effective for clinical response (0.71 and 0.70 respectively), with amoxicillin-clavulanate plus macrolides and beta-lactams being less effective (p-score 0.11 and 0.22). Quinolones were most likely to be associated with lower mortality (0.63). All confidence intervals were broad and partially overlapping. We observed trends toward a better clinical response and lower mortality for quinolones as empiric antibiotics for CAP, but found no conclusive evidence of any antibiotic being clearly more effective than another. More trials are needed to inform guideline recommendations on the most effective antibiotic regimens for outpatients with mild to moderate CAP.

1646. Optimizing Antibiotic Durations of Therapy in Pediatric Community-acquired Pneumonia

Abstract Background Several recent high-quality studies have shown similar efficacy for a shorter, 5-day duration of antibiotics instead of the prior standard, 10 days, in pediatric community-acquired pneumonia (CAP). Despite high-quality literature support, implementing short courses into routine clinical practice remains challenging. This study aimed to assess the impact on the duration of antibiotics for CAP of a pilot clinical pharmacist discharge antibiotic prescription review and departmental education supporting short-course antibiotics for CAP. Methods This was a single-center retrospective cohort study for patients admitted with an order for any antimicrobial for CAP. Patients were excluded if they were admitted to the pediatric intensive care unit or transferred during their course of care. The pre-intervention period was from June 2021 to June 2022, and the postintervention group was from August to October 2022. A one-time education session was hosted with the Pediatric Hospital Medicine department summarizing the literature supporting short courses. Statistical analysis included ANOVA, Fisher’s Exact, and Mann-Whitney U test as appropriate. Results One hundred twenty-four patients were included, 85 in the pre-intervention and 39 in the post-intervention groups. The median age was two years old in both groups (p=0.2). No differences were present in the median length of stay, penicillin-allergy status, or vaccination status. Patients had a positive viral test 56% and 59%, respectively (p=0.8). Discharge attendings did differ and impact the total length of therapy (p&amp;lt; 0.001). Overall median antibiotic duration for CAP decreased from 8 to 5 days (p&amp;lt; 0.01). Inpatient median durations remained the same at 2 days (p=0.5), while outpatient durations fell from 6 to 4 days (p&amp;lt; 0.01). Patients that received over seven days for CAP decreased from 62% to 10% (p&amp;lt; 0.01). Treatment failure at 30 days occurred in 2 and 8% (p=0.16), respectively. Conclusion A pilot discharge prescription review by clinical pharmacists and education supporting short courses for CAP effectively reduced the duration of antibiotic therapy. Consideration should be given to discharge antibiotic prescription reviews when adopting short courses for common pediatric infections. Disclosures Shubho Sarkar, MD, Abbott Laboratories: Stocks/Bonds|Abbvie INC: Stocks/Bonds|Bristol-Myers Squibb: Stocks/Bonds|CVS Health Corp: Stocks/Bonds|Johnson &amp; Johnson: Stocks/Bonds

Electronic phenotyping of community-acquired pneumonia: A tool for inpatient syndrome-specific antimicrobial stewardship

Background: Using patient data from the electronic health record (EHR) and computer logic, an “electronic phenotype” can be created to identify patients with community-acquired pneumonia (CAP) in real time to assist with syndrome-specific antimicrobial stewardship efforts.1 We adapted and validated the performance of an inpatient CAP electronic phenotype for antimicrobial stewardship interventions. Methods: An automated scoring system was created within the EHR (Epic Systems) to identify hospitalized patients with CAP based on the variables and logic listed in Fig. 1B. We adapted a score used by the Michigan Hospital Medicine Safety Consortium (HMS) to identify patients with CAP, with additions made to improve sensitivity (Fig. 1).1 The score can be displayed in a column within the EHR patient list (Fig. 2). We validated the electronic phenotype via chart review of all hospitalized patients on systemic antimicrobials admitted to a medicine team consecutively between November 8 and 18, 2021. Patients who were readmitted within the validation time frame were excluded. We assessed the performance of the electronic phenotype by comparing the score to manual chart review, where “CAP diagnosis” was defined as (1) mention of “pneumonia” or “CAP” as part of the differential diagnosis in the admission documentation, (2) antimicrobials were started within 48 hours of admission, and (3) radiographic findings were suggestive of pneumonia. After initial evaluation, the scoring system was adjusted, and performance was re-evaluated during prospective audit and feedback performed on EHR CAP–positive patients over 13 days between July 2022 and December 2022. Results: We included 191 patients in our initial validation cohort. The CAP score had high sensitivity (95.83%), specificity (92.2%), and negative predictive value (99.35%), though lower positive predictive value (63.89%) was noted (Table 2). The rules were further refined to include bloodstream infection only with Haemophilus influenza or Streptococcus pneumoniae in rule 2B, and azithromycin was removed from “CAP antibiotics.” After these changes, repeated evaluation of 88 patients with positive CAP EHR score was performed, and only 20 (23%) were considered false-positive results. Conclusions: Electronic phenotypes can be used to create automated tools to identify patients with CAP with reasonable performance. Data from this tool can be used to guide more focused antimicrobial stewardship interventions and clinical decision support in the future. Reference: Vaughn VM, et al. A statewide collaborative quality initiative to improve antibiotic duration and outcomes in patients hospitalized with uncomplicated community-acquired pneumonia. Clin Infect Dis 2022;75:460–467.Disclosures: None

Optimal duration of antibiotic treatment for community-acquired pneumonia in adults: a systematic review and duration-effect meta-analysis

ObjectivesTo find the optimal treatment duration with antibiotics for community-acquired pneumonia (CAP) in adults.DesignSystematic review and duration-effect meta-analysis.Data sourcesMEDLINE, Embase and CENTRAL through 25 August 2021.Eligibility criteriaAll randomised controlled trials...

554. Discharge Antibiotic Prescribing at Children’s Hospitals with Established Antimicrobial Stewardship Programs

Abstract Background Antibiotic stewardship programs optimize antibiotic use in hospitalized children, but most do not routinely review antibiotic prescriptions at discharge. Up to 30% of discharged children receive additional days of antibiotics, and one single-center study found that 27% of discharge prescriptions were suboptimal. Methods We conducted a retrospective cohort study to evaluate duration of therapy (DOT) and antibiotic choice for children &amp;lt; 18 years admitted to 4 children’s hospitals from January 1, 2019 - December 31, 2019 and prescribed antibiotics at discharge for uncomplicated community-acquired pneumonia (CAP), skin and soft tissue infection (SSTI), or urinary tract infection (UTI). We excluded children with complex medical conditions, &amp;gt; 1 infection requiring antibiotics, &amp;gt; 7 day hospital stay, or intensive care unit stay. The primary outcomes were the percentage of subjects prescribed optimal (1) total (inpatient plus outpatient) DOT (4-6 days for CAP and SSTI, ≤8 days for UTI), and (2) antibiotic choice (CAP: amoxicillin; SSTI: clindamycin, amoxicillin-clavulanate, cephalexin, or trimethoprim-sulfamethoxazole (TMP/SMX); UTI: cephalexin, amoxicillin, amoxicillin-clavulanate, TMP/SMX, or nitrofurantoin) based on current national guidelines and available evidence. Results 2105 encounters were included: 783 CAP, 916 SSTI, and 406 UTI. Median age was 4 years and 49% were female. DOT for each condition are shown in Figure 1 and antibiotic choice in Figure 2. Antibiotic choice was optimal for 66% with CAP, 98% with SSTI, and 88% with UTI. DOT was optimal for 11% with CAP, 4% with SSTI, and 21% with UTI. Both DOT and choice were optimal for 2% with CAP, 4% with SSTI, and 19% with UTI. For all indications, antibiotic choice was optimal for 84% and DOT was optimal for 10%, while only 6% of antibiotic courses included both optimal DOT and antibiotic choice. Total duration of therapy for 2105 children discharged with antibiotics for community-acquired pneumonia, urinary tract infection, and skin and soft tissue infection. Figure 1.Median duration of antibiotic therapy prescribed for 783 children with community-acquired pneumonia, 406 with urinary tract infection, and 916 with skin and soft tissue infection. The box and whiskers within each plot depict the median (white dot), interquartile range (box) and 5th/95th percentiles (whiskers); the width of each plot represents the number of courses that received that value for overall antibiotic duration. Discharge antibiotic choices for 2105 children with community-acquired pneumonia, urinary tract infection, and skin and soft tissue infection. Figure 2.The most commonly prescribed antibiotics at discharge for 2105 children with community-acquired pneumonia, urinary tract infection, or skin and soft tissue infection. Percentages based on total number of antibiotic prescriptions. Other antibiotics include: Cefadroxil, Cefdinir, Cefixime, Doxycycline, Levofloxacin, Linezolid, Nitrofurantoin, trimethoprim-sulfamethoxazole. Conclusion At 4 children’s hospitals with established antimicrobial stewardship programs, 94% of discharge antibiotic courses for CAP, UTI, and SSTI were suboptimal either by choice of antibiotic or duration of therapy. Discharge antibiotic prescribing represents a significant opportunity to improve antibiotic use in children. Disclosures Jason Newland, MD, AHRQ: Grant/Research Support|Merck: Grant/Research Support|NIH: Grant/Research Support|PEW Charitable Trust: Grant/Research Support|Pfizer: Grant/Research Support.

Disseminated Coccidioidomycosis in an Immunocompetent Male Who Lived in an Endemic Region in the Remote Past: A Case Report

Coccidioidomycosis is an endemic illness suspected in patients who live in or have recently traveled to an endemic area. Disseminated disease is less frequent and is almost always seen in the presence of risk factors such as immunosuppression. We present a case of disseminated coccidioidomycosis with a delayed presentation in a young immunocompetent male. The patient developed symptoms two years after migrating from the endemic region of Mexico. He presented with fever, cough, and shortness of breath for two weeks. Chest imaging revealed left-sided consolidation and pleural effusion. Empyema was ruled out by thoracentesis. The patient did not improve with antibiotics for community-acquired pneumonia. A comprehensive microbiological workup for bacterial, viral, mycobacterial, and fungal etiologies, including cultures of several specimens of sputum, pleural fluid, blood, bronchoalveolar lavage, serological tests (initial), and transbronchial lung biopsy, was nondiagnostic. The patient continued to have fever and shortness of breath despite the escalation of antibiotic coverage to broad-spectrum. The patient underwent an open surgical lung biopsy, and the diagnosis of coccidioidomycosis was ultimately established by histopathological examination of lung and pleural specimen which showed spherules of Coccidioides sp. The patient developed worsening headaches, a lumbar puncture was done and cerebrospinal fluid revealed coccidioidal antibody which confirmed meningeal dissemination. Human immunodeficiency virus/acquired immunodeficiency syndrome or other immunosuppressed state was not identified in the patient. Notably, the second set of antibody titers collected two weeks after the initial negative set of titers returned strongly positive. The patient was started on fluconazole but did not show clinical improvement and was switched to amphotericin B. Subsequently, the patient improved and was discharged on lifelong oral fluconazole with close outpatient clinical and serological monitoring. He has had no signs of relapse during the last 20 months.

A little education goes a long way: Decreasing antibiotics for community-acquired pneumonia in COVID-19 patients

Background: Antibiotic use was common in patients with suspected or confirmed COVID-19 infection; however, data emerged demonstrating low rates of bacterial coinfection (6%–10%). Antimicrobial stewardship best practice was challenged during this time, requiring new strategies and education to limit the inappropriate use of antibiotics. At the Veterans’ Affairs Maryland Healthcare System, we evaluated the use of community acquired pneumonia (CAP) specific antibiotics in COVID-19–positive patients after successive interventions. Methods: We conducted a pre–post evaluation of common CAP antibiotics (ceftriaxone IV/IM, cefpodoxime PO, azithromycin PO/IV, ampicillin/sulbactam IV, amoxicillin-clavulanate PO, levofloxacin) during the COVID-19 pandemic. The preintervention period was April–October 2020 and the postintervention period was November 2020–April 2021. During the preintervention period, intervention A was carried out as follows: (1) inpatient weekly virtual interdisciplinary COVID-19 rounds were led by an antimicrobial stewardship champion, (2) χprocalcitonin was implemented in clinical decision making, and (3) inpatient audit and feedback of active antibiotics was conducted by the antimicrobial stewardship team. In the postintervention period, intervention B was added as follows: (1) weekly educational COVID-19 virtual seminars were conducted for providers, and (2) targeted education was provided to emergency department and hospitalist directors. Comparisons of the proportions of antibiotics prescribed were made between the pre- and postintervention periods using X2 statistic, and data were stratified by location. The rates of CAP antibiotic prescription per 100 COVID-19–positive patients were also compared using Poisson distribution. Results: During the study period, 814 unique patients had COVID-19 infection: 182 (22.4%) patients admitted to the acute-care center, 66 (8.1%) long-term care residents, and 566 (69.5%) were managed outside the hospital. Of these 814 patients, 211 (25%) were prescribed a CAP antibiotic. Of the antibiotics prescribed, 223 (61%) were ceftriaxone, cefpodoxime, amoxicillin-clavulanate, or ampicillin-sulbactam; 123 (34%) were azithromycin; and 16 (4.4%) were levofloxacin. We observed a decrease in the frequency of all antibiotic prescriptions after intervention B was added: 32% (86 of 273) vs 23% (125 of 541) (P = .01). Decreases in antibiotic prescriptions were observed in all locations: acute care (57% vs 44%), long-term care (53% vs 41%) and outpatient care (19% vs 15%). The rates of CAP antibiotic prescribing per 100 COVID-19–positive patients were 114 in the preintervention period and 45 in the postintervention period, a rate difference of −70 antibiotics per 100 COVID-19–positive patients (pConclusions: Curbing antibiotic use for CAP indication during the COVID-19 pandemic was a challenge. A multifaceted approach focusing on education was an impactful intervention leading to significant decreases in antibiotic prescribing despite COVID-19 cases increasing.Funding: NoneDisclosures: None

Peripartum Severe COVID-19 Pneumonia: Fetal and Neonatal Implications.

Peripartum Severe COVID-19 Pneumonia: Fetal and Neonatal Implications.

CHEST IN CRISIS: A CASE OF BRONCHOBILIARY FISTULA

TOPIC: Signs and Symptoms of Chest Diseases TYPE: Medical Student/Resident Case Reports INTRODUCTION: Bronchobiliary fistula (BBF) is a rare occurrence of altered anatomy of the biliary duct system in which it connects to the lungs. Biliptysis is pathognomonic for this condition. Predisposing factors include malignancy, bile duct obstruction, trauma, and surgery. Our case highlights a patient who presented with several months of non-resolving right middle lobe (RML) pneumonia who was later found to have a BBF. CASE PRESENTATION: Our patient is a 43-year-old male with a history of colon cancer with liver metastasis on palliative chemotherapy who presented after multiple episodes of RML pneumonia. He had endoscopic retrograde cholangiopancreatography (ERCP) with stent placement for malignant biliary obstruction. Three months later, he had fever, cough, and scant yellow sputum with chest x-ray (CXR) findings of RML consolidation. He received appropriate antibiotics for community-acquired pneumonia. His symptoms recurred two weeks later. During that admission, the CT chest showed consolidation of the RML. Sputum culture grew Klebsiella pneumoniae and was treated appropriately. He had two more similar episodes. Bronchoscopy showed erythematous endobronchial mucosa in the RML with carbapenem-resistant Enterobacteriaceae (CRE) and Klebsiella pneumoniae on culture. Transbronchial lung biopsy was negative for malignancy. After seven months from the initial ERCP, he presented with copious bilious sputum and right pleuritic chest pain. Repeat CT chest showed persistent RML consolidation and 4 cm fluid collection along the hepatic capsule which grew CRE and Klebsiella pneumoniae. This raised suspicion for bronchobiliary fistula. A hepatobiliary iminodiacetic acid (HIDA) scan done did not demonstrate the presence of a fistula. Magnetic resonance cholangiography (MRC) was done which showed a small sinus tract that represented a BBF. He underwent right anterior sectionectomy of the liver with diaphragm repair and ERCP with replacement of biliary stent. DISCUSSION: The most common cause of acquired BBF is liver malignancy likely through obstruction which produces inflammation in the subdiaphragmatic space with subsequent rupture into the bronchial system. Patients can present with pneumonia, while it is rare, it is the most common comorbidity associated with BBF. Our patient presented with biliptysis and recurrent pneumonia with multidrug-resistant organisms. MRC and HIDA are preferred studies as they are non-invasive. Our patient's HIDA scan was not diagnostic but the MRC showed the BBF. Our patient underwent segmental hepatectomy and ERCP with stent replacement with subsequent symptom resolution. CONCLUSIONS: A high index of suspicion is required to diagnose BBF when the presentation is atypical such as in the case of recurrent RML pneumonia. Early diagnosis is important to prevent progressive antibiotic resistance. Non-invasive modalities like HIDA and MRC are preferred for making the diagnosis. REFERENCE #1: Liao G-Q. Management of acquired bronchobiliary fistula: A systematic literature review of 68 cases published in 30 years. World J Gastroenterol. 2011;17(33):3842. doi:10.3748/wjg.v17.i33.3842 REFERENCE #2: Aduna M, Larena JA, Martín D, Martínez-Guereñu B, Aguirre I, Astigarraga E. Bile duct leaks after laparoscopic cholecystectomy: value of contrast-enhanced MRCP. Abdom Imaging. 2005;30(4):480-487. doi:10.1007/s00261-004-0276-2 DISCLOSURES: No relevant relationships by Tundun babalola, source=Web Response No relevant relationships by Afoma King, source=Web Response No relevant relationships by Nirvi Shah, source=Web Response No relevant relationships by susan waitimu, source=Web Response

Comparing Several Treatments with Antibiotics for Community-Acquired Pneumonia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background:We aimed to review relevant randomized controlled trials to assess the relative clinical effects of antibiotic treatment of patients with community-acquired pneumonia (CAP).Methods:In this meta-analysis, we identified relevant studies from PubMed, Cochrane, and Embase using appropriate keywords. Key pertinent sources in the literature were also reviewed and all articles published through Oct 2019 were considered for inclusion. For each study, we assessed the risk ratios (RRs) or mean difference combined with the 95% confidence interval (CI) to assess and synthesize outcomes.Results:Overall, 36 studies were consistent with the meta-analysis, involving 17,076 patients. There was no significant difference in the mortality after subgroup analysis: individualized treatment vs. standard treatment; β-lactams plus macrolides vs. β-lactam and/or fluoroquinolone; ceftaroline fosamil vs. ceftriaxone; combination therapy vs. monotherapy or high-dose vs. low-dose. The drug-related adverse event incidence was significantly higher in the ceftriaxone group than in the other drug groups (P<0.05) and also higher in the tigecyline group than in the levofloxacin group (P<0.05). Compared with ceftriaxone, ceftaroline fosamil significantly increased the clinical cure rate at the test-of-cure (TOC) visit in the clinically evaluable population, modified intent-to-treat efficacy (MITTE) population, microbiologically evaluable (ME) population and the microbiological MITTE (mMITTE) population (all P<0.05). Compared with ceftriaxone, ceftaroline fosamil significantly increased the clinical cure rate at the TOC visit in the mMITTE population of Gram positive-Streptococcus pneumoniae (P<0.05) and multidrug-resistant S. pneumoniae (P<0.05).Conclusion:There was a limited number of included studies in the subgroup analysis, but it will still be necessary to conduct more high-quality randomized controlled trials to confirm the clinical efficacy of different antibiotics used to treat CAP.

Antibiotics for CAP: Narrow-Spectrum on the Rise

Source: Lipsett SC, Hall M, Ambroggio L, et al. Antibiotic choice and clinical outcomes in ambulatory children with community-acquired pneumonia. J Pediatr. 2021;229:207-215.E1; doi./10.1016/j.jpeds.2020.10.005Investigators from multiple institutions conducted a retrospective cohort study to assess antibiotic-prescribing patterns and clinical outcomes among children diagnosed with community-acquired pneumonia (CAP). Children were eligible if they were 1-18 years old, had an outpatient claim in the MarketScan Medicaid Database from 2010–2016 with a diagnosis of CAP, and had a prescription filled for an oral antibiotic within a day after the index visit. Patient age, visit setting (ED or outpatient clinic), visit during influenza season, asthma history, and presence of chronic conditions were obtained from the Medicaid database.The primary exposure was antibiotic type, categorized as narrow-spectrum (eg, aminopenicillins), broad-spectrum (eg, amoxicillin/clavulanate, cephalosporins), macrolide monotherapy (eg, azithromycin), narrow-spectrum agents in combination with a macrolide, and broad-spectrum agents in combination with a macrolide. The primary outcome was a claim for hospitalization for any reason 2-7 days after the index visit. A secondary outcome was severe pneumonia, defined as ICU admission, a chest drainage procedure, or death occurring 2-7 days after the index visit. Investigators used multivariable logistic regression to assess the odds of each outcome based on antibiotic type adjusted for age, number of chronic conditions, visit setting, visit during influenza seasons, and asthma co-diagnosis during the index visit. A sub-analysis was conducted excluding children with asthma, given the potential benefit of macrolides to them.There were 252,177 children included in analysis. Overall, macrolide monotherapy was prescribed in 43.2%, narrow-spectrum antibiotics in 26.1%, and broad-spectrum antibiotics in 24.7%. Macrolide use decreased over time (45.8% in 2010 to 40.5% in 2016; P <0.001) while narrow-spectrum antibiotic prescribing increased (20.1% in 2010 to 31.8% in 2016; P <0.001).A total of 1,488 children (0.69%) were hospitalized, and 117 (0.05%) developed severe pneumonia. Compared to children who received narrow-spectrum antibiotics, hospitalization was significantly higher among children who received broad-spectrum antibiotics and lower among children who received macrolide monotherapy. The absolute difference in hospitalization rate between children on narrow-spectrum and macrolide monotherapy was small, however (0.6% vs 0.4%, respectively). The odds of developing severe pneumonia were lower in children receiving macrolide monotherapy compared to those who received narrow-spectrum antibiotics, though this difference became statistically insignificant when excluding participants with asthma.The investigators conclude that macrolides are the most commonly prescribed antibiotic for CAP despite national guidelines emphasizing the use of narrow-spectrum antibiotics.Dr Brady has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.The current investigators assessed adherence to the 2011 clinical practice guideline-recommended antibiotic therapies for children with CAP.1 Amoxicillin is recommended as first-line antibiotic therapy for previously healthy, appropriately immunized infants, preschool children, school-aged children, and adolescents with mild to moderate CAP suspected to be of bacterial origin. Macrolides are recommended primarily for school-aged children and adolescents when an atypical pathogen (eg, Mycoplasma pneumoniae) is suspected.1 Alternative antibiotic recommendations are provided for those with penicillin allergy.Immunization status and penicillin allergy were not assessed in the current study. Focusing on children 1-4 years of age, 34% received amoxicillin. Lack of receipt of age-appropriate immunizations for Streptococcus pneumoniae, the most common bacterial cause of CAP in this age group,1-2 and penicillin allergy probably did not fully account for receipt of antibiotics other than aminopenicillins. About 33% received macrolide monotherapy despite concerns that 20% to 40% of S. pneumoniae isolates are resistant to macrolides3 and atypical pathogens are uncommon causes of CAP in children <5 years.4 Over the study period, there was an 18% increase in narrow-spectrum antibiotic prescribing in the 1-4 years group, but improvement is still needed, especially among children enrolled in Medicaid.Compared to children who received narrow-spectrum antibiotics, hospitalization was significantly higher among children who received broad-spectrum antibiotics, although the absolute difference was small. This finding is not intuitive, and therefore potential explanations need to be considered. Clinicians may have chosen broad-spectrum antibiotics initially for children they believed to be at higher risk of needing later hospitalization. Another point to consider is that certain broad-spectrum antibiotics (eg, second-and third-generation oral cephalosporins) provide adequate activity against only 60% to 70% of isolated strains of S. pneumoniae.1 Hence, they may be less effective than narrow-spectrum, high-dose amoxicillin if the child has CAP due to pneumococcus. The “take home” message was that initial use of broad-spectrum antibiotics did not prevent hospitalizations.Although macrolides are commonly prescribed, most children with CAP improve with narrow-spectrum oral amoxicillin (for outpatients) or IV ampicillin (for inpatients). (See AAP Grand Rounds. 2019;41[6]:65.)5Given the vagaries of diagnosis of pneumonia vs no pneumonia and the lack of definitive identification of a pathogen in the vast majority of cases, it is not surprising that the results of this study do not support current guideline recommendations for management of CAP.

Antibiotics prescriptions for pneumonia analyzed by claim information in Japan

OBJECTIVE Japan is an aging society, and pneumonia is the leading cause of death, but the suitability of antibiotics for treating community-acquired pneumonia (CAP) in Japan is not clear. The purpose of this study was to investigate antibacterial drugs for treating CAP according to age. MATERIALS AND METHODS Using the Japanese national database from 2011 to 2014, we analyzed the usage of antibiotics for CAP according to age. RESULTS The numbers of claim information were 9,386, and 70% of the patients were aged ≥ 75 years. Sulbactam/ampicillin (SBT/ABPC) or ceftriaxone (CTRX) was used in 60%, but broad-spectrum antibiotics, combination therapy, and anti-mycoplasma antibiotics were used in 15 - 28% of all age groups. The 30-day survival rate did not differ between SBT/ABPC or CTRX vs. others. There was no difference in 30-day mortality and risk in any group between the ages of 15 and 64 years. On the other hand, the use of anti-mycoplasma antibiotics reduced the 30-day mortality by 0.50 times (p < 0.01), and the use of two or more antibiotics increased the 30-day mortality by 1.45 times (p = 0.02) at age ≥ 65 years. CONCLUSION Approximately half of the antibiotics used for CAP requiring hospitalization consisted of CTRX or SBT/ABPC as recommended by the Japanese Respiratory Society (JRS) guidelines. On the other hand, the usage of broad-spectrum antibiotics and combination therapy were relatively frequent at all ages, although their use does not always contribute to survival. Our data provide basic information for analyzing the outcome of pneumonia treatment in terms of an antimicrobial resistance action plan in Japan.

Half of all hospitalised children treated with antibiotics for pneumonia did not fulfil radiological, microbiological or laboratory criteria.

Evaluating the management of paediatric pneumonia is important. We aimed to estimate the proportion of children receiving antibiotics for suspected community-acquired pneumonia (CAP) that were likely to have a bacterial infection. Furthermore, we described antibiotic use in relation to guidelines. We conducted a prospective observational study from a paediatric department in Norway. During 2017, all admitted children aged 0-17years receiving antibiotics for CAP were enrolled in the study. We collected relevant data and defined likely CAP as one or more of the following: radiologically confirmed pneumonia, c-reactive protein of at least 100mg/L, positive bacterial culture from blood or pleura, detection of bacteria from the nasopharynx associated with atypical pneumonia. In total, 70 episodes of suspected CAP were included. Median age was 41.5months, and 36 (51%) were girls. Of all treatments, 38 (54%) fulfilled our criteria for likely CAP. Median duration of treatment was 10days. Of empirical treatments, 36 (57%) only involved penicillin. None of the children had neutropenia or complications, and only two needed intensive care. Only half of children receiving antibiotics for suspected CAP were likely to have bacterial infection. Despite no obvious reason, antibiotic treatment was longer than currently recommended.

803. Risk factors associated with Clostridioides difficile infection in hospitalized patients with community-acquired pneumonia

BackgroundPatients with community-acquired pneumonia (CAP) who are hospitalized and treated with antibiotics may carry an increased risk for developing Clostridioides difficile infection (CDI). Accurate risk estimation tools are needed to guide monitoring and CDI mitigation efforts. We aimed to identify patient-specific risk factors associated with CDI among hospitalized patients with CAP.MethodsDesign: retrospective case-control study of hospitalized patients who received CAP-directed antibiotic therapy between 1/1/2014 and 5/29/2018. Cases were hospitalized CAP patients who developed CDI post-admission. Control patients did not develop CDI and were selected at random from CAP patients hospitalized during this period. Variables: comorbidities, laboratory results, vital signs, severity of illness, prior hospitalization, and past antibiotic use. Propensity-score weights: identified via structural decomposition analysis of pre-treatment variables. Analysis: weighted classification tree models that predicted any CDI, hospital-onset CDI, and any healthcare-associated CDI according to CAP antibiotic treatment. Performance: percent accuracy in classification (PAC) and weighted positive (PPV) and negative predictive values (NPV). Modeling: completed using the ODA package (v1.0.1.3) for R (v3.5.1).ResultsA total of 32 cases and 232 controls were identified. Sixty pre-treatment variables were screened. Structural decomposition analysis, completed in two stages, identified prior hospitalization (OR 6.56, 95% CI: 3.01-14.31; PAC: 80.3%) and BUN greater than 29 mg/dL (OR 11.67, 95% CI: 2.41-56.5; PAC: 80.8%) as propensity-score weights. With respect to CDI, receipt of broad-spectrum anti-pseudomonal antibiotics was significantly (all P’s< 0.05) associated with any CDI (NPV: 90.29%, PPV: 27.94%), hospital-onset CDI (NPV: 97.53%, PPV: 26.86%), and healthcare-associated CDI (NPV: 92.89%, PPV: 27.94%).ConclusionWe identified risk factors available at hospital admission and empiric use of broad-spectrum Gram-negative antibiotics as being associated with the development of CDI. Model PPVs were over two-fold greater than our sample base rate. Increased monitoring and avoidance of overly broad antibiotic use in high-risk patients appears warranted.Disclosures All Authors: No reported disclosures

Investigational and Experimental Drugs for Community-Acquired Pneumonia: the Current Evidence.

Community-acquired pneumonia (CAP) is a common infection with a constantly evolving etiological spectrum. This changing etiology conditions the adequate selection of optimal therapeutic regimens, both in empirical and definitive treatments. In recent years, new antimicrobials have been approved by regulatory authorities for use in CAP, although it is necessary to continue incorporating new antimicrobial agents that improve the activity profile in relation to the appearance of bacterial resistance in certain pathogens, such as pneumococcus, Staphylococcus aureus or Pseudomonas aeruginosa. Delafloxacin, omadacycline and lefamulin are the most recently approved antibiotics for CAP. These three antibiotics have shown non-inferiority to their comparators for the treatment of CAP with an excellent safety profile. However, in the 2019 ATS/IDSA guidelines, it has been considered that more information is needed to incorporate these new drugs into community-based treatment. New antimicrobials, such as solithromycin and nemonoxacin, are currently being studied in Phase III clinical trials. Both drugs have shown non-inferiority against the comparators and an acceptable safety profile; however, they have not yet been approved by the regulatory authorities. Several drugs are being tested in Phase I and II clinical trials. These include zabofloxacin, aravofloxacin, nafithromycin, TP-271, gepotidacin, radezolid, delpazolid, and CAL02. The preliminary results of these clinical trials allow us to assure that most of these drugs may play a role in the future treatment of CAP.

2066. Development and Implementation of Prescribing Algorithms for Antibiotics on Discharge from the Emergency Department

BackgroundIn the emergency department (ED), rapid decision-making and frequent distractions are often challenging to implementing effective antimicrobial stewardship. The purpose of this project is to improve guideline adherence and promote optimal use of outpatient antibiotic therapy for community-acquired infections.MethodsPrescribing algorithms were developed to integrate clinical practice guideline recommendations with emergency department-specific antibiogram data. Algorithms for treating community-acquired pneumonia (CAP), skin and soft-tissue infections (SSTI), and urinary tract infections (UTI) were made available throughout the ED. Outcomes were evaluated through a chart review of patients prescribed empiric outpatient antibiotics for CAP, SSTI, or UTI by ED providers. Patients were excluded if they were <18 years old, pregnant, or taking antibiotics prior to arrival. The primary outcome was rate of adherence to clinical practice guidelines, defined as the selection of an appropriate antibiotic agent, dose, and duration of therapy for each patient discharged. Secondary outcomes included the rate of fluoroquinolone use, as well as all-cause 30-day returns to the ED or urgent care.ResultsWhen compared with patients discharged from the ED prior to algorithm implementation (N = 325), the post-implementation group (N = 172) received more antibiotic prescriptions that were completely guideline adherent (57.0% vs. 11.7%, P < 0.01). Post-implementation discharge orders demonstrated improvement in the selection of an appropriate agent (86.6% vs. 45.5%, P < 0.01), dose (89.0% vs. 77.2%, P < 0.01), and duration of therapy (63.4% vs. 39.1%, P < 0.01). Additionally, fluoroquinolone prescribing rates in this population were reduced (2.9% vs. 12.3%, P < 0.01). In the post-implementation patients who presented at least 30 days prior to analysis (N = 124), a reduction in all-cause 30-day returns to the ED or urgent care was observed (12.9% vs. 21.5%, P < 0.05).ConclusionImplementation of antibiotic prescribing algorithms improved guideline adherence in the outpatient treatment of CAP, SSTI, and UTI. By developing prescribing algorithms, pharmacists may reduce the unnecessary use of broad-spectrum antibiotics and prevent patient returns to the ED.Disclosures All authors: No reported disclosures.

Lefamulin—A New Antibiotic for Community-Acquired Pneumonia

Lefamulin—A New Antibiotic for Community-Acquired Pneumonia

Expecting the unexpected.

e14066 Background: Myasthenia gravis is an autoimmune neuro-muscular disorder traditionally seen in bi-modal distribution in young women or older men. Discovery of immunotherapy has brought hope in survival outcomes for patients with malignant melanoma, lung, renal and head/neck cancers but it also opens Pandora’s box of immune-related toxicities for which early recognition and appropriate clinical management are paramount. Here we describe a case of immunotherapy induced myasthenia gravis de novo. Methods: A 77-year-old man with HPV+ stage IVA squamous cell carcinoma of the tongue presented with sudden onset orthopnea and dyspnea on exertion for the past day. One week ago, he received his second cycle of nivolumab as part of his neoadjuvant therapy. He was seen at an outside hospital and was found to be acute hypercapnic respiratory failure and placed on BiPAP. He was started on antibiotics for community-acquired pneumonia with levofloxacin and doxycycline and transferred to a tertiary care center for further management. On further evaluation, he endorsed diplopia, blurry vision, fluctuating muscle weakness that is worse at the end of the day, change in voice and proximal muscle weakness. His exam was consistent with bilateral ptosis, weak hip flexion and shoulder abduction, positive sniff test and poor vital capacity and negative inspiratory force values suggestive of impending respiratory and diaphragmatic failure secondary to myasthenic crisis. He was admitted to the ICU and placed on BiPAP and frequent NIF and VC monitoring. He was started on pyridostigmine but showed no clinical improvement on day 1 and hence was initiated on plasmapheresis from day 2 for a total of 10 days. Results: Investigations showed positivity of Ach-R modulating and binding and blocking antibodies with negative voltage gated calcium channel antibodies. EMG revealed decrement of the compound muscle action potential in the repetitive stimulation test indicative of myasthenia gravis. He responded well to the above treatment and underwent successful left partial glossectomy and weaned off mechanical ventilation and has been cancer free so far. He is doing well on maintenance prednisone and pyridostigmine. Conclusions: There is a significant 30.4% MG-specific-related mortality due to immunotherapy alone which this case demonstrates the importance of vigilance and early detection for effective treatment and management. It highlights need for the oncological world and our colleagues in various other disciplines of healthcare to identify and mitigate the effects of immunotherapy which has become our hope in beating cancer.

New antibiotics for community-acquired pneumonia

This review provides the rationale for the development of new antibiotics to treat community-acquired pneumonia (CAP). It also provides an overview of the new antibiotics targeting CAP that have recently received approval by the regulatory agencies, and those antibiotics that are in the development pipeline. CAP is one of the most common reasons for hospitalization and carries a significant morbidity and risk of mortality. Increasing antibiotic resistance amongst the common bacterial pathogens associated with CAP, especially staphylococci and Streptococcus pneumoniae, has made the empiric treatment of this infection increasingly problematic. Moreover, failure of initial empiric therapy to cover the causative agents associated with CAP can be associated with worse clinical outcomes. There have been several antibiotics newly approved or in development for the treatment of CAP. These agents include delafloxacin, omadacycline, lefamulin, solithromycin, nemonoxacin, and ceftaroline. Their major advantages include activity against methicillin-resistant Staphylococcus aureus and macrolide-resistant Strep. pneumoniae. CAP continues to be an important infection because of its impact on patient outcomes especially in the elderly and immunocompromised hosts. The availability of new antibiotics offers an opportunity for enhanced empiric treatment of the antibiotic-resistant bacterial pathogens associated with CAP.