Broad-spectrum Antimicrobial Therapy Research Articles

Use of broad-spectrum antimicrobials for more than 72 h and the detection of multidrug-resistant bacteria in Japanese intensive care units: a multicenter retrospective cohort study

BackgroundLarge multicenter studies reporting on the association between the duration of broad-spectrum antimicrobial administration and the detection of multidrug-resistant (MDR) bacteria in the intensive care unit (ICU) are scarce. We evaluated the impact of broad-spectrum antimicrobial therapy for more than 72 h on the detection of MDR bacteria using the data from Japanese patients enrolled in the DIANA study.MethodsWe analyzed the data of ICU patients in the DIANA study (a multicenter international observational cohort study from Japan). Patients who received empirical antimicrobials were divided into a broad-spectrum antimicrobial group and a narrow-spectrum antimicrobial group, based on whether they received broad-spectrum antimicrobials for more or less than 72 h, respectively. Differences in patient characteristics, background of infectious diseases and empirical antimicrobial administration, and outcomes between the two groups were compared using the chi-square tests (Monte Carlo method) for categorical variables and the Mann–Whitney U-test for continuous variables. We also conducted a logistic regression analysis to investigate the factors associated with the detection of new MDR bacteria.ResultsA total of 254 patients from 31 Japanese ICUs were included in the analysis, of whom 159 (62.6%) were included in the broad-spectrum antimicrobial group and 95 (37.4%) were included in the narrow-spectrum antimicrobial group. The detection of new MDR bacteria was significantly higher in the broad-spectrum antimicrobial group (11.9% vs. 4.2%, p = 0.042). Logistic regression showed that broad-spectrum antimicrobial continuation for more than 72 h (OR [odds ratio] 3.09, p = 0.047) and cerebrovascular comorbidity on ICU admission (OR 2.91, p = 0.041) were associated with the detection of new MDR bacteria.ConclusionsAmong Japanese ICU patients treated with empirical antimicrobials, broad-spectrum antimicrobial usage for more than 72 h was associated with the increased detection of new MDR bacteria. Antimicrobial stewardship programs in ICUs should discourage the prolonged use of empirical broad-spectrum antimicrobial therapy.Trial registration ClinicalTrials.gov, NCT02920463, Registered 30 September 2016, https://clinicaltrials.gov/ct2/show/NCT02920463

P215 Investigation of an outbreak of neonatal Candida emia in the NICU of a 300 -bedded hospital in North India

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMObjectivesNeonatal Candidaemia causes significant morbidity and mortality in very low birth weight neonates. We report the occurrence of an outbreak of neonatal Candidaemia due to Candida krusei in the neonatal intensive care unit (NICU) of a 300-bedded hospital in North India.MethodsA total of 96 blood cultures from 80 neonates admitted in the NICU from October 2020 to April 2021 were received and processed manually in the Microbiology lab. A total of 5 among the 47 yeast isolates were sent to a teaching hospital for identification and antifungal susceptibility testing by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF). Clinical parameters (very low birth weight, gestational age, birth asphyxia, broad-spectrum antimicrobial therapy, intra-uterine growth restriction, and total parenteral nutrition), lab parameters (CRP, platelet count), and patient outcome were evaluated. A total of 26 environmental samples and hand swabs from six health care workers were collected to trace the source of the outbreak. The samples were inoculated on 5% sheep blood agar and MacConkey agar. Regular rounds of the NICU and training sessions were conducted by the infection control team to intensify the infection control measures.ResultsBlood culture results: In all, 57 neonates (71.25%; 57/80) admitted to the NICU had positive blood cultures. A total of 47 blood cultures yielded non-albicans Candida spp. (82.45%; 47/57). The other microorganisms isolated from blood cultures were Pseudomonas aeruginosa (4), MRSA (3), Klebsiella pneumoniae (4) and Acinetobacter baumanni (1). Polymicrobial bloodstream infections were detected in two neonates. All the yeast isolates subjected to MALDI-TOF were identified as Candida krusei and had similar MICs of 0.25, 4, 16, 1, 0.25 and 16 μg/ml for voriconazole, itraconazole, posaconazole, caspofungin, micafungin and fluconazole respectively.Culture results of environmental sampling: Yeast could not be isolated from any environmental sample and hand swabs of health care workers. However, MRSA was isolated from the hands of one health care worker.Observation during the infection control rounds:Sterile gauze pieces soaked in iodine and kept in plastic bottles were being used for skin antisepsis before collecting samples or before introducing an IV cannula.The nursing staff did not wear sterile gloves while collecting blood samples or introducing IV cannula in case of NICU patients.It was observed that the used bottles of IV fluids (eg. Ringer lactate, normal saline) were not capped and kept at room temperature.Intensive infection control measures and training sessions were effective in controlling the outbreak.ConclusionWe report the occurrence of a massive outbreak of neonatal Candidaemia in the NICU of our hospital with a positivity rate of 58.75% (47/80). Identification of yeast and determination of antifungal susceptibility is important for prompt treatment. Though the source of the outbreak could not be traced but intensifying infection control practices could control the outbreak. This study emphasizes the value of educating healthcare workers and regular monitoring of disinfection practices to prevent health-care-associated infections.

Safety of De-Escalating Empiric Antimicrobial Agents in Trauma Patients with Indigenous Oral Flora Ventilator-Associated Pneumonia.

Background: Ventilator-associated pneumonia (VAP) is a frequently occurring nosocomial infection in critically ill trauma patients. When bronchoalveolar lavage (BAL) returns with indigenous oral flora (IOF), de-escalating antimicrobial therapy is challenging. Patients and Methods: This is a retrospective review of trauma patients who received broad-spectrum empiric antimicrobial therapy for clinical VAP, and whose BAL culture resulted with >100,000 CFU/mL of IOF from September 1, 2017 to September 1, 2020. Patients were identified using the trauma database and microbiology reports of BALs with IOF. This review evaluated the effect of antibiotic de-escalation on recurrent or persistent pneumonia. Results: Of 51 trauma patients with clinical VAP and IOF, 18 patients (35.3%) had antimicrobial agents de-escalated. De-escalation was driven primarily by the discontinuation of vancomycin, with the continuation of a β-lactam antibiotic as monotherapy for the remainder of the treatment course (n = 15; 86.7%). The overall rate of either persistent or recurrent VAP in the cohort was 10%, and this did not differ statistically between those who received de-escalation therapy after isolation of IOF and those who did not (16.7% vs. 6.1%; p = 0.224), however, the incidence of acute kidney injury (AKI) was higher in the non-de-escalation group (39.4% vs. 11.1%; p = 0.034). There was no statistical difference in ventilator days, intensive care unit (ICU) length of stay, or hospital length of stay between treatment groups. Conclusions: Trauma patients who develop VAP with isolated BAL cultures of IOF or mixed flora can safely have anti-methicilllin-resistant Staphylococcus aureus (MRSA) antimicrobial agents discontinued, and this may result in decreased rates of AKI.

Microbiological analysis of peritoneal fluid samples from patients with perforated peptic ulcer – retrospective observational study

Peritonitis due to perforated peptic ulcer (PPU) is a surgical emergency associated with high mortality. Preoperative management includes immediate initiation of broad-spectrum antimicrobial therapy. The objective of this study was to assess the spectrum of microbial pathogens in peritoneal fluid. Retrospective observational study of patients who underwent surgery for PPU at the 1st Department of Surgery - Thoracic, Abdominal and Injury Surgery, General University Hospital in the period 2015-2020. Analysis of the microbiological analytical results of peritoneal fluid. The microbiological profile of PPU-associated peritonitis is somewhat different from microbial pathogens involved in secondary peritonitis due to bowel perforation. A high rate of negative culture findings, high incidence of Candida spp. and low incidence of anaerobic bacteria are characteristic for PPU-associated peritonitis. Negative culture from the peritoneal fluid collected during surgery was identified in 42% of the patients. A total of 66 isolates of microbial pathogens were identified, including Candida spp. (42.5%), aerobic gram-positive bacteria (30.3%), aerobic gram-negative bacteria (22.7%) and anaerobic bacteria (4.5%). Candida albicans and Candida glabrata represented the most common species. Decreased susceptibility to fluconazole and resistance to itraconazole was associated with all Candida glabrata isolates. Although PPU-associated peritonitis is mostly of community origin, we confirmed a significant incidence of Candida spp. with decreased azole susceptibility. The choice of antifungal therapy should always be based on local epidemiology.

Potential Impact of Rapid Multiplex PCR on Antimicrobial Therapy Guidance for Ventilated Hospital-Acquired Pneumonia in Critically Ill Patients, A Prospective Observational Clinical and Economic Study.

ObjectivesTo investigate the potential impact of the syndromic multiplex FilmArray® Pneumonia plus Panel (FAPP) on the antimicrobial treatment guidance of patients with ventilated hospital-acquired pneumonia (VHAP).MethodsRespiratory fluids from 100 adult patients with VHAP, receiving invasive mechanical ventilation in three intensive care units from one French university hospital, were tested prospectively using FAPP. Conventional cultures were performed in parallel as routine practice. Clinicians were left blinded to the FAPP results. Antimicrobial therapies based on FAPP results were simulated by independent blinded experts according to a predefined algorithm and compared to 1) those prescribed in practice according to local guidelines (real-life), and 2) those that complied with the international ERS/ESICM/ESCMID/ALAT recommendations. The primary endpoint was the number of days of broad-spectrum antimicrobial therapy. Secondary endpoints were the rates of microbiological treatment failure and cost-effectiveness ratio.ResultsThe predicted median duration of broad-spectrum antibiotics was 0 [0-1.25] day in the FAPP-based simulation, versus 2 [0-6] days in real-life (p<0.0001) and 2 [2-3.25] days in the recommendations-based simulation (p<0.0001). Treatment failure was predicted in 3% of cases with FAPP results versus observed in 11% in real-life (p=0.08) and 6% with recommendations-based simulation (p=0.37). The incremental cost-effectiveness ratio was 1 121 € [-7021; 6794] to avoid one day of non-optimized antimicrobial therapy.ConclusionsOur results suggest that using FAPP in patients with VHAP has the potential to reduce the use of broad-spectrum antimicrobial therapy without increasing the risk of microbial treatment failure.

Pneumocephalus and Suppurative Meningoencephalitis in a Dog after Craniofacial Trauma

Background: Pneumocephalus is characterized by the presence of gas in the intracranial compartment, and it can develop because of trauma or craniofacial surgery or spontaneously. Clinical signs start within days or months after the injury and vary according to the site of involvement. Computed tomography is the ideal diagnostic tool, however skull radiography can also be used. Treatment varies according to the severity of the case, and it can be conservative or associated with surgical intervention in the most severe cases. The purpose of this report is to describe the case of a dog that developed pneumocephalus and suppurative meningoencephalitis after head trauma caused by a bite from another dog. Case: A 2-month-old bitch, mixed breed, with 3.2 kg, was referred to the veterinary hospital because it had been bitten on the head by another dog. Shortly after the incident, the animal showed no clinical signs. However, 2 days later, the bitch became depressed and in persistent lateral decubitus. A lesion with a crust of approximately 0.5 cm was found close to the occipital region, with bone irregularity on palpation. The animal was in lateral decubitus with muscular hypotonia, bilateral mydriasis unresponsive to light and stupor. Radiographic images showed parietal fracture and pneumocephalus. Based on the findings of physical and laboratorial exams, diagnosis of suppurative meningoencephalitis and pneumocephalus secondary to craniofacial trauma was established. Empirical broad-spectrum antimicrobial therapy was started in addition to mannitol, corticoids, and analgesics. The animal was referred for surgical debridement by trepanation, when samples were collected to bacterial culture, which was negative. Despites the care, the animal died 14 h after the surgical procedure. Histopathological examination of the frontal cortex was performed, being the histological changes compatible with suppurative meningoencephalitis. Discussion: Dog bites on the head and neck are particularly severe, and can create intracranial bleeding, disfigurement of the face, damage to peripheral structures or cranial fractures. In this report, through radiographic images, it was found that the patient had an intracerebral aerocele, since there was presence of gas in the intracranial compartment. This alteration should always be considered in animals with neurological alterations and a history of craniofacial trauma. The main neurological changes observed in the reported case were unresponsive to mydriasis and altered mental status 2 days after the trauma, and this delay in the onset of clinical signs is frequently reported in cases of pneumocephalus. Neutrophilia and leukocytosis observed can be justified by the suppurative meningoencephalitis, confirmed by the histopathological exam. Antimicrobial therapy should be started as soon as possible, and the choice must be based on their capacity to cross the blood-brain barrier and the broad spectrum. The administration of antibiotics before collecting the material for bacterial culture may explain the negative result of this test, so that it is not possible to determine whether the intracranial gas observed on the radiograph may have developed from the trauma or because of gas-producing bacteria. Head trauma can induce suppurative meningoencephalitis and pneumocephalus even in the absence of perforating wounds at the time of the consultation. The neurological signs can start days after the trauma. Besides the clinical and surgical treatments, the prognosis of any bacterial infection of the central nervous system is poor. Keywords: aerocele, brain syndrome, Glasgow scale, radiography, trepanation.

Low diagnostic yield and time to diagnostic confirmation results in prolonged use of antimicrobials in critically ill children.

Background: Broad-spectrum antimicrobial therapy is a key driver of antimicrobial resistance. Here, we aimed to review indications for antimicrobial therapy, determine the proportion of suspected bacterial infections that are confirmed by culture, and assess the time taken for microbiology test results to become available in the paediatric intensive care unit (PICU). Methods: A single-centre prospective observational cohort study of 100 consecutive general PICU admissions from 30 October 2019 to 19 February 2020. Data were collected from the hospital medical record and entered into a study database prior to statistical analysis using standard methods. Results: Of all episodes of suspected infection, 22% of lower respiratory tract infection, 43% of bloodstream and 0% of central nervous system infection were associated with growth on microbiology culture. 90% of children received antimicrobial therapy. Hospital-acquired infection occurred less commonly than primary infection, but an organism was grown in a greater proportion (64%) of cultures. Final laboratory reports for negative cultures were issued at a median of 120.3 hours for blood cultures and 55.5 hours for endotracheal tube aspirate cultures. Conclusions: Despite most critically children receiving antimicrobial therapy, infection was often not microbiologically confirmed. Novel molecular diagnostics may improve rationalisation of treatment in this population.

Low diagnostic yield and time to diagnostic confirmation results in prolonged use of antimicrobials in critically ill children

Background: Broad-spectrum antimicrobial therapy is a key driver of antimicrobial resistance. Here, we aimed to review indications for antimicrobial therapy, determine the proportion of suspected bacterial infections that are confirmed by culture, and assess the time taken for microbiology test results to become available in the paediatric intensive care unit (PICU). Methods: A single-centre prospective observational cohort study of 100 consecutive general PICU admissions from 30 October 2019 to 19 February 2020. Data were collected from the hospital medical record and entered into a study database prior to statistical analysis using standard methods. Results: Of all episodes of suspected infection, 22% of lower respiratory tract infection, 43% of bloodstream and 0% of central nervous system infection were associated with growth on microbiology culture. 90% of children received antimicrobial therapy. Hospital-acquired infection occurred less commonly than primary infection, but an organism was grown in a greater proportion (64%) of cultures. Final laboratory reports for negative cultures were issued at a median of 120.3 hours for blood cultures and 55.5 hours for endotracheal tube aspirate cultures. Conclusions: Despite most critically children receiving antimicrobial therapy, infection was often not microbiologically confirmed. Novel molecular diagnostics may improve rationalisation of treatment in this population.

The efficacy and safety of fenticonazole in the treatment of mixed vaginitis

Background: Vaginitis means inflammation of the vaginal mucosa and is one of the most common causes for consulting to a gynecologists. Mixed-type vaginal infections are simultaneous infections of at least two types of vaginal pathogens (for example, a bacteria and a Candida species). In the treatment of mixed vaginitis, broad spectrum antimicrobial therapy effective on different kinds of pathogens is required. Aim: The purpose of this review is to evaluate the place and efficacy of fenticonazole nitrate (2% vaginal cream and 600 mg pessary forms) in mixed-type vaginitis. Method: Literatures were retrieved by a PubMed search, using different combinations of pertinent keywords (e.g., fenticonazole, fungal infection, mixed vaginal infections), without any limitations in terms of publication date and language. Papers which assessed the therapeutic efficacy and tolerability of fenticonazole in patients with mixed vaginitis were selected for inclusion according to their relevance for the topic, as judged by the authors. Results: Fenticonazole has a broad spectrum of activity, including antifungal, antibacterial and antiparasidic effects. Fenticonazole nitrate provides significant improvement in symptoms such as vaginal discharge, pruritus and burning associated with candidal vulvovaginitis, with a cure rate of 97.5%. In addition, while fenticonazole provides 85% cure rates in bacterial vaginitis, it is an effective topical option with a clinical cure rate of 87% in mixed vulvovaginal infections with Candida albicans, Gardnerella vaginalis and/ or Trichomonas vaginalis. Fenticonazole provides up to 90% improvement in symptoms such as pruritus, burning, redness, discharge and edema, which are frequently observed in vaginitis, with its rapid onset of action and excellent tolerability from the first days of treatment. Conclusion: Fenticonazole has a broad spectrum of antimicrobial activity with its antifungal, antibacterial and antiparasidic effects. It is an ideal topical alternative with its high clinical efficacy in Candidal vulvovaginitis caused by Candida albicans, bacterial vaginosis caused by Gardnerella vaginalis, gram (+) and/or gram (-) bacteria, and Trichomonal vaginitis caused by Trichomonas vaginalis and mixed vaginitis caused by these pathogens and its excellent tolerability. Fenticonazole has lower efficacy against the three main lactobacillus strains called Lactobacillus gasseri, Lactobacillus jensenii and Lactobacillus crispatus found on the vaginal flora compared to miconazole and metronidazole with high MID rates. Fenticonazole is a treatment option with efficacy, safety and excellent tolerability that can be the first choice empirically in the first-line treatment of mixed-type vaginitis, which has been shown to be effective in fungal, bacterial and mixed-type vaginal infections with its broad spectrum of action in various clinical studies.

Empiric antimicrobial therapy for early-onset pneumonia in severe trauma patients.

The bacterial ecology involved in early pneumonia of severetrauma patients is mostly commensal and would allow wide use of narrow-spectrum antibiotics. We describe risk factors for treatment failure of severe trauma patients' pneumonia with the use of narrow-spectrum antimicrobial therapy in orderto develop a score that could help clinicians to determine which patients might be treated with narrow-spectrum antibiotics. A retrospective, observational, monocentric cohort study was conducted of severe trauma patients requiring mechanical ventilation for > 48h and developing a first episode of microbiologically confirmed pneumonia occurring within the first 10 days after admission. Overall, 370 patients were included. The resistance rate against narrow-spectrum antibiotics (amoxicillin/clavulanic acid) was 22.7% (84 pneumonia). In a multivariate analysis, two independent risk factors were associated with this resistance: prior antimicrobial therapy ≥ 48h (OR 4.00; 95 CI [2.39; 6.75]) and age ≥ 30y (OR 2.10; 95 CI [1.21; 3.78]). We created a prediction score that defined patient with one or two risk factors at high risk of resistance. This score presented a sensitivity of 0.92 [0.88; 0.94], a specificity of 0.33 [0.28; 0.38], a positive predictive value of 0.29 [0.24; 0.33] and a negative predictive value of 0.93 [0.90; 0.95]. Simple risk factors may help clinicians to identify severe trauma patients at high risk of pneumonia treatment failure with the use of narrow-spectrum antimicrobial therapy and, thus, use better tailored empiric therapy and limit the use of unnecessary broad-spectrum antimicrobial therapy.

Diagnostic Dilemma and Therapeutic Challenges in Managing an Atypical Presentation of an Ocular Toxoplasmosis Patient With Myasthenia Gravis: Literature Review

Purpose The aim of the study was to report a case of ocular toxoplasmosis (OT) in an immunocompromised patient with myasthenia gravis, the diagnostic dilemma, and therapeutic challenges in managing the patient. Method This is a case report with literature review. Articles reviewed were limited to publications in English, and there were no restrictions on date, age, ethnicity, or geographic locations of patients. In addition, a brief literature review of similar reported cases was conducted to discuss about the diagnostic dilemma and therapeutic challenges in managing our patient. Observation We report a case of an immunocompromised, 53-year-old man who presented with rapid deterioration of left eye vision for 2 weeks. The ophthalmological examination showed nongranulomatous panuveitis with dense vitritis and retinitis with the absence of adjacent pigmented scar. Diagnostic dilemma arose as the clinical picture mimicked several possible etiologies. He was initially treated clinically as viral retinitis but failed to show improvement with antiviral treatment. Because of recent history of left empyema, he was then treated as presumed endophthalmitis and received broad-spectrum antimicrobial and antifungal therapies. He was also given oral sulfamethoxazole and trimethoprim (Bactrim) because of suspicion on OT. Despite multiple drug therapy, he still did not improve clinically. A diagnostic pars plana vitrectomy was performed and the toxoplasma polymerase chain reaction was positive. Therapeutic challenges were apparent due to limited choice of antibiotics which can be used in patients with myasthenia gravis and possible resistance to Bactrim in this case. After 6 weeks of pyrimethamine and sulfadiazine, he was clinically stable with vision of 6/60 due to macular scarring. Conclusions The diagnosis of atypical OT is challenging and frequently misdiagnosed as viral retinitis or endophthalmitis, leading to delayed diagnosis and treatment. Clinicians should have a high index of suspicion whenever seeing an atypical manifestation of OT in immunocompromised patients. In addition, there is very limited published data looking into the clinical presentations, diagnostic methods, treatment modalities and outcomes, specifically in reported atypical OT case reports or series. Therefore, it warrants an in-depth review to help clinician have a better understanding about this disease.

58. Impact of Order-set Modifications and Provider Education on Broad-Spectrum Antibiotic Use in Patients Admitted with Community Acquired Pneumonia

BackgroundFollowing updates to IDSA guidelines in 2019, Hartford HealthCare implemented changes to the community acquired pneumonia (CAP) order-set in August 2020 to reflect criteria for prescribing of broad-spectrum antimicrobial therapy. The objective of the study was to evaluate changes in broad-spectrum antibiotic days of therapy (DOT) following these order-set updates with accompanying provider education.MethodsThis was a multi-center, quasi-experimental, retrospective study of patients with CAP from 9/1/19 to 10/31/19 (pre-intervention) and 9/1/20 to 10/31/20 (post-intervention). Patients were identified using ICD-10 codes indicating lower respiratory tract infection and excluded if had a positive SARS-COV-2 PCR during admission. Data collected included demographics, labs and vitals, radiographic, microbiological, and antibiotic data. The primary outcome was change in broad-spectrum antibiotic DOT, specifically anti-pseudomonal β-lactams and anti-MRSA antibiotics. Secondary outcomes included guideline-concordance of initial antibiotics, utilization of an order-set to prescribe antibiotics, and length of stay (LOS).ResultsA total of 331 and 352 patients were included in the pre- and post-intervention groups, respectively. The overall duration of broad-spectrum therapy was a median of 2 days (IQR 0-8 days) in the pre-intervention period and 0 days (IQR 0-4 days) in the post-intervention period (p< 0.001). Patients in whom the order-set was used in the post-intervention period were more likely to have guideline-concordant regimens ([36/40] 90% vs. [190/312] 60.9%; p = 0.003). There were no differences in order set usage (10% vs. 11.3%, p = 0.642) between the pre- and post-intervention groups, respectively. Hospital LOS was lower in the post-intervention cohort (4.8 days [2.9-7.2 days] vs. 5.3 days [IQR 3.5-8.5 days], p = .002). ConclusionDespite low utilization of the order-set, education surrounding order-set changes appeared to improve antibiotic prescribing and hospital LOS in our population. Further opportunities to improve order-set use and thus further increase guideline-concordant therapy are still available. Disclosures Joseph L. Kuti, PharmD, Allergan (Speaker’s Bureau)BioMérieux (Consultant, Research Grant or Support, Speaker’s Bureau)Contrafect (Scientific Research Study Investigator)GSK (Consultant)Merck (Research Grant or Support)Paratek (Speaker’s Bureau)Roche Diagnostics (Research Grant or Support)Shionogi (Research Grant or Support)Summit (Scientific Research Study Investigator) David P. Nicolau, PharmD, Abbvie, Cepheid, Merck, Paratek, Pfizer, Wockhardt, Shionogi, Tetraphase (Other Financial or Material Support, I have been a consultant, speakers bureau member, or have received research funding from the above listed companies.)

Impact of Order-Set Modifications and Provider Education Following Guideline Updates on Broad-Spectrum Antibiotic Use in Patients Admitted With Community Acquired Pneumonia.

Purpose: Following updates to the Infectious Diseases Society of America (IDSA) practice guidelines for the Diagnosis and Treatment of Adults with Community-acquired Pneumonia in 2019, Hartford HealthCare implemented changes to the community acquired pneumonia (CAP) order-set in August 2020 to reflect criteria for the prescribing of broad-spectrum antimicrobial therapy. The objective of the study was to evaluate changes in broad-spectrum antibiotic days of therapy (DOT) following these order-set updates with accompanying provider education. Methods: This was a multi-center, quasi-experimental, retrospective study of patients with a diagnosis of CAP from September 1, 2019 to October 31, 2019 (pre-intervention) and September 1, 2020 to October 31, 2020 (post-intervention). Patients were identified using ICD-10 codes (A48.1, J10.00-J18.9) indicating lower respiratory tract infection. Data collected included demographics, labs and vitals, radiographic, microbiological, and antibiotic data. The primary outcome was change in broad-spectrum antibiotic DOT, specifically anti-pseudomonal β-lactams and anti-MRSA antibiotics. Secondary outcomes included guideline-concordance of initial antibiotics, utilization of an order-set to prescribe antibiotics, and length of stay (LOS). Results: A total of 331 and 352 patients were included in the pre- and post-intervention cohorts, respectively. There were no differences in order-set usage (10% vs 11.3%, P = .642) between the pre- and post-intervention cohort, respectively. The overall duration of broad-spectrum therapy was a median of 2 days (IQR 0-8 days) in the pre-intervention period and 0 days (IQR 0-4 days) in the post-intervention period (P < .001). Patients in whom the order-set was used in the post-intervention period were more likely to have guideline-concordant regimens ([36/40] 90% vs [190/312] 60.9%; P = .003). Hospital LOS was shorter in the post-intervention cohort (4.8 days [2.9-7.2 days] vs 5.3 days [IQR 3.5-8.5 days], P = .002). Conclusion: Implementation of an updated CAP order-set with accompanying provider education was associated with reduced use of broad-spectrum antibiotics. Opportunities to improve compliance and thus further increase guideline-concordant therapy require investigation.

A detailed neuropathological assessment of a Western Australian case of Balamuthia mandrillaris amoebic encephalitis

Balamuthia mandrillaris is a protist, amphizoic protozoan that is free-living in the soil. This amoebae can rarely cause cutaneous disease and an amoebic encephalitis, the time-course of which ranges from subacute to fulminant.1 A 76-year-old male presented with a 1 week history of fevers and rigors, progressing rapidly to weakness with confusion and a GCS of 13 but without localising neurological signs. MRI brain and spine reported diffuse parenchymal and leptomeningeal disease, most marked within the median frontal lobes, favouring an infective/ haemorrhagic meningoencephalitis. No causative microorganism was identified on ante mortem investigation. Despite broad spectrum antimicrobial therapies, the patient deteriorated clinically. Brain death occurred 10 days after the initial presentation and the case was referred to the State Coroner’s Office of WA. Post mortem examination diagnosed Balamuthia mandrillaris infection which was confirmed by PCR testing of brain tissue and cerebrospinal fluid. This report details the neuropathological distribution of parenchymal cerebral necrosis, associated with trophozoite and encysted amoebic forms, which suggests a haematogenous portal of entry for the protozoa into the brain. We present detailed neuropathology findings on the third case of Balamuthia mandrillaris encephalitis originating in Western Australia to be reported in the literature. 1.Siddiqui R, Khan NA. Balamuthia mandrillaris: morphology, biology and virulence. Trop Parasitol 2015; 5: 15–22.

Low diagnostic yield and time to diagnostic confirmation results in prolonged use of antimicrobials in critically ill children

Background: Broad-spectrum antimicrobial therapy is a key driver of antimicrobial resistance. Here, we aimed to review indications for antimicrobial therapy, determine the proportion of suspected bacterial infections that are confirmed by culture, and assess the time taken for microbiology test results to become available in the paediatric intensive care unit (PICU). Methods: A single-centre prospective observational cohort study of 100 consecutive general PICU admissions from 30 October 2019 to 19 February 2020. Data were collected from the hospital medical record and entered into a study database prior to statistical analysis using standard methods. Results: Of all episodes of suspected infection, 22% of lower respiratory tract infection, 43% of bloodstream and 0% of central nervous system infection were associated with growth on microbiology culture. 90% of children received antimicrobial therapy. Hospital-acquired infection occurred less commonly than primary infection, but an organism was grown in a greater proportion (64%) of cultures. Final laboratory reports for negative cultures were issued at a median of 120.3 hours for blood cultures and 55.5 hours for endotracheal tube aspirate cultures. Conclusions: Despite most critically children receiving antimicrobial therapy, infection was often not microbiologically confirmed. Novel molecular diagnostics may improve rationalisation of treatment in this population.

Characterization of respiratory microbial dysbiosis in hospitalized COVID-19 patients

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of Coronavirus disease 2019 (COVID-19). However, the microbial composition of the respiratory tract and other infected tissues as well as their possible pathogenic contributions to varying degrees of disease severity in COVID-19 patients remain unclear. Between 27 January and 26 February 2020, serial clinical specimens (sputum, nasal and throat swab, anal swab and feces) were collected from a cohort of hospitalized COVID-19 patients, including 8 mildly and 15 severely ill patients in Guangdong province, China. Total RNA was extracted and ultra-deep metatranscriptomic sequencing was performed in combination with laboratory diagnostic assays. We identified distinct signatures of microbial dysbiosis among severely ill COVID-19 patients on broad spectrum antimicrobial therapy. Co-detection of other human respiratory viruses (including human alphaherpesvirus 1, rhinovirus B, and human orthopneumovirus) was demonstrated in 30.8% (4/13) of the severely ill patients, but not in any of the mildly affected patients. Notably, the predominant respiratory microbial taxa of severely ill patients were Burkholderia cepacia complex (BCC), Staphylococcus epidermidis, or Mycoplasma spp. (including M. hominis and M. orale). The presence of the former two bacterial taxa was also confirmed by clinical cultures of respiratory specimens (expectorated sputum or nasal secretions) in 23.1% (3/13) of the severe cases. Finally, a time-dependent, secondary infection of B. cenocepacia with expressions of multiple virulence genes was demonstrated in one severely ill patient, which might accelerate his disease deterioration and death occurring one month after ICU admission. Our findings point to SARS-CoV-2-related microbial dysbiosis and various antibiotic-resistant respiratory microbes/pathogens in hospitalized COVID-19 patients in relation to disease severity. Detection and tracking strategies are needed to prevent the spread of antimicrobial resistance, improve the treatment regimen and clinical outcomes of hospitalized, severely ill COVID-19 patients.

524 Use of Broad-Spectrum Antibiotics and Sepsis-3 Criteria in Burns

Abstract Introduction Sepsis is a diagnostic challenge in critically ill patients; especially so in the burn population because the signs and symptoms of sepsis are pervasive after injury. The Sepsis-3 criteria identify organ dysfunction as an acute change in SOFA score ≥ 2 points consequent to infection. The objective of this study was to evaluate if Sepsis-3 criteria were fulfilled when broad-spectrum antimicrobial therapy was started in a burn cohort. Methods We included all adult (≥ 18 years) patients with an acute burn admitted to our burn centre within 2 days of injury between 2016 and 2019. Only patients that received meropenem or piperacillin/tazobactam during their acute hospitalization period were included. Patients were stratified based on the Sepsis-3 definition using evidence of infection and evaluation of organ failure in the 48-hour period prior to the administration of antibiotics. Results We studied 70 patients, with 24 patients in the control group and 46 patients in the Sepsis-3 group. Demographics were similar among the control and Sepsis-3 groups: mean age was 44 ± 18 versus 48 ± 18 years (p=0.372); but injury severity was significantly different: median percent TBSA burn 18% vs. 32% (p=0.003) and proportion of inhalation injury 13% vs. 50% (p=0.002). Length of stay (LOS) was significantly longer in the Sepsis-3 group, control group median 23 days vs. median 43 days (p&amp;lt; 0.001). However, LOS/TBSA was not significantly different in the control group compared to the Sepsis-3 group: median 1.6 vs. 1.4 days per percent TBSA burn (p=0.777). Mortality was similar among the groups: 13% vs. 20% (p=0.526). The proportion of patients diagnosed by a physician with sepsis was also similar with 21% in the control group vs. 33% in the Sepsis-3 group (p=0.406). Conclusions Though the Sepsis-3 group had greater injury severity, mortality, and LOS in-hospital, when normalized to TBSA, was similar. Patients were diagnosed by a physician with sepsis in less than a third of cases. This raises the question of why broad-spectrum antibiotics were started. Potentially, patients were treated based on clinical suspicion of sepsis instead of delaying treatment until diagnosis was confirmed. Benefits of early antibiotic administration must be considered in conjunction with antimicrobial stewardship.

Recurrent and Complicated Urinary Tract Infection in Type 2 Diabetes

Urinary tract infection (UTI) is a common infection in patients with type 2 diabetes (T2DM). We present a case series of recurrent and complicated UTI requiring hospitalization in people with T2DM. Recurrence of UTI, especially when severe or complicated, causes multiple renal and extra renal complications and even death if not intervened early. Recurrent UTI is often caused by resistant pathogens in people with long duration of diabetes and uncontrolled glucose levels. In recurrent and complicated/severe UTI, empirical broad-spectrum antimicrobial therapy and early urological intervention will help early recovery and helps to prevent complications.

P0585 / #619: CO-INFECTIONS IN SEVERE DENGUE - HOW COMMON IS IT?

Aims & Objectives: Dengue is the most common mosquito borne viral infection in the world. Concomitant infections in children with dengue are known to occur but are uncommon. The purpose of this study was to determine the prevalence of coexistent infections in children admitted with severe dengue to PICU. Methods: All children admitted to PICU from January 2016 to December 2019 with severe dengue, confirmed by serology and NS1 were included in the study. Data were collected through a retrospective review of the medical records and the frequency of co-infections was determined. Results: A total of 189 children with a median age of 54 months (IQR 10-99 months) were admitted with severe dengue during the 4 year period. Dengue was confirmed by both NS1 and serology (IgM). Scrub typhus and malaria co-infection were present in 3/189 children and 2/189 respectively. 61% (116/189) of children received empirical antibiotics. Of the 116 children, antibiotics were de-escalated in 80% (93/116) after 48 hours negative blood culture results. Final blood culture results in all children were reported negative. Overall mortality of the group was 5% (10/189). Conclusions: Our study shows that co-infections are very uncommon in children with severe dengue. Hence it is important to re-evaluate and de-escalate empiric broad-spectrum antimicrobial therapy after initial (48 hour) blood culture results.

Prevent deterioration and long-term ventilation: intensive care following thoracic surgery.

Patients with indication for lung surgery besides the pulmonary pathology often suffer from independent comorbidities affecting several other organ systems. Preventing patients from harmful complications due to decompensation of underlying organ insufficiencies perioperatively is pivotal. This review draws attention to the peri- and postoperative responsibility of the anaesthetist and intensivist to prevent patients undergoing lung surgery deterioration. During the last decades we had to accept that 'traditional' intensive care medicine implying deep sedation, controlled ventilation, liberal fluid therapy, and broad-spectrum antimicrobial therapy because of several side-effects resulted in prolongation of hospital length of stay and a decline in quality of life. Modern therapy therefore should focus on the convalescence of the patient and earliest possible reintegration in the 'life-before.' Avoidance of sedative and anticholinergic drugs, early extubation, prophylactic noninvasive ventilation and high-flow nasal oxygen therapy, early mobilization, well-adjusted fluid balance and reasonable use of antibiotics are the keystones of success. A perioperative interprofessional approach and a change in paradigms are the prerequisites to improve outcome and provide treatment for elder and comorbid patients with an indication for thoracic surgery.