Use Of Spectrum Antibiotics Research Articles

Genomic profiling of pan-drug resistant proteus mirabilis Isolates reveals antimicrobial resistance and virulence gene landscape

Proteus mirabilis is a gram-negative pathogen that caused significant opportunistic infections. In this study we aimed to identify antimicrobial resistance (AMR) genes and virulence determinants in two pan-drug resistant isolate “Bacteria_11” and “Bacteria_27” using whole genome sequencing. Proteus mirabilis “Bacteria_11” and “Bacteria_27” were isolated from two different hospitalized patients in Egypt. Antimicrobial susceptibility determined using Vitek 2 system, then whole genome sequencing (WGS) using MinION nanopore sequencing was done. Antimicrobial resistant genes and virulence determinants were identified using ResFinder, CADR AMR database, Abricate tool and VF analyzer were used respectively. Multiple sequence alignment was performed using MAFFT and FastTree, respectively. All genes were present within bacterial chromosome and no plasmid was detected. “Bacteria_11” and “Bacteria_27” had sizes of approximately 4,128,657 bp and 4,120,646 bp respectively, with GC content of 39.15% and 39.09%. “Bacteria_11” and “Bacteria_27” harbored 43 and 42 antimicrobial resistance genes respectively with different resistance mechanisms, and up to 55 and 59 virulence genes respectively. Different resistance mechanisms were identified: antibiotic inactivation, antibiotic efflux, antibiotic target replacement, and antibiotic target change. We identified several genes associated with aminoglycoside resistance, sulfonamide resistance. trimethoprim resistance tetracycline resistance proteins. Also, those responsible for chloramphenicol resistance. For beta-lactam resistance, only blaVEB and blaCMY-2 genes were detected. Genome analysis revealed several virulence factors contribution in isolates pathogenicity and bacterial adaptation. As well as numerous typical secretion systems (TSSs) were present in the two isolates, including T6SS and T3SS. Whole genome sequencing of both isolates identify their genetic context of antimicrobial resistant genes and virulence determinants. This genomic analysis offers detailed representation of resistant mechanisms. Also, it clarifies P. mirabilis ability to acquire resistance and highlights the emergence of extensive drug resistant (XDR) and pan-drug resistant (PDR) strains. This may help in choosing the most appropriate antibiotic treatment and limiting broad spectrum antibiotic use.

Management of Clostridioides difficile infection: an Italian Delphi consensus.

Clostridioides difficile infection (CDI), a leading cause of nosocomial deaths, is a microbiota-mediated disease. As such, the use of broader spectrum antibiotics, such as vancomycin and metronidazole, can prime the gastrointestinal tract to become more prone to CDI recurrences. Fidaxomicin, a narrow-spectrum antibiotic, has been demonstrated to be superior in preventing recurrence and in preserving the intestinal microbiota; however, widespread employment worldwide has been hindered due to high acquisition costs. To integrate the currently available guidelines on the management of CDI and to shed light on the timeliest employment of fidaxomicin. An expert panel was gathered to obtain consensus using Delphi methodology on a series of statements regarding the management of CDI and on appropriate antibiotic use. Consensus was reached on 21 of the 25 statements addressing the management of CDI. Delphi methodology was used to achieve consensus on the management of CDI, on the identification of patients at risk of recurrences or severe infection, and on the most appropriate use of fidaxomicin, with the final aim of fostering clinical practice application of treatment algorithms proposed by previous guidelines, in absolute synergy. It could be an important tool to promote more appropriate and cost-effective CDI treatments in European settings with limited resources, like Italy.

Laboratory Tests, Bacterial Resistance, and Treatment Options in Adult Patients Hospitalized with a Suspected Urinary Tract Infection.

Patients treated for systemic urinary tract infections commonly have nonspecific presentations, and the specificity of the results of the urinalysis and urine cultures is low. In the following narrative review, we will describe the widespread misuse of urine testing, and consider how to limit testing, the disutility of urine cultures, and the use of antibiotics in hospitalized adult patients. Automated dipstick testing is more precise and sensitive than the microscopic urinalysis which will result in false negative test results if ordered to confirm a positive dipstick test result. There is evidence that canceling urine cultures if the dipstick is negative (negative leukocyte esterase, and nitrite) is safe and helps prevent the overuse of urine cultures. Because of the side effects of introducing a urine catheter, for patients who cannot provide a urine sample, empiric antibiotic treatment should be considered as an alternative to culturing the urine if a trial of withholding antibiotic therapy is not an option. Treatment options that will decrease both narrower and wider spectrum antibiotic use include a period of watching and waiting before antibiotic therapy and empiric treatment with antibiotics that have resistance rates > 10%. Further studies are warranted to show the option that maximizes patient comfort and safety.

94. Rapid Diagnostic Testing is Associated with Decreased Broad Spectrum Antibiotic Use in Streptococcal Blood Stream Infections

Abstract Background Rapid diagnostic testing (RDT) allows antimicrobial stewardship programs (ASP) to intervene early in the setting of sepsis and septic shock leading to lower rates of death. Combining RDT with ASP results in faster antibiotic de-escalation compared to RDT alone; however, the utility of this approach for Streptococcal bacteremia is unproven. The objective of this study was to evaluate the impact of RDT with real-time ASP intervention on blood cultures growing Streptococcal species. Methods Retrospective, observational study comparing patients with Streptococcus spp. bacteremia over two 6-month periods. During the pre-RDT period, patients were prospectively followed by ASP who provided recommendations based on gram-stain and organism identification results. During the post-RDT period, blood cultures were tested by GenMark ePlex BCID-GP that identifies S. agalactiae, S. anginosis group, S. pneumoniae, S. pyogenes and Streptococcus spp. within 90 minutes which were reported directly to ASP for recommendations on antibiotic discontinuation, de-escalation, and additional diagnostic testing. Results 94 patients were included in the analysis, 50 pre- and 44 post-RDT. Across cohorts, patient demographics, clinical characteristics, and severity of illness were comparable (Table 1). The median ages were 58 and 56, 62% and 68% were men, and a total of 12% and 16% were immunocompromised. The mean qSOFA scores were 1.9 and 2. The most common Streptococcus spp. was S. mitis (figure 1). Prior to RDT, the median time to antibiotic de-escalation was 88 hours. Following implementation of RDT, median time to de-escalation was 42 hours (P=0.002). De-escalation to targeted therapy improved from 50% to 86% in post-RDT (P< 0.01). Transition to oral antibiotics increased from 14% to 30% (P=0.08). There were no differences in hospital re-admission or acute kidney injury. A trend toward decreased 30-day mortality was identified in the post-RDT period (P=0.06). Conclusion Our study highlights the impact of RDT with ASP intervention on clinical outcomes for patients with Streptococcal bacteremia. We noted significant reductions in broad-spectrum antibiotic use and a trend towards lower mortality. Larger studies are needed to demonstrate the full potential of this approach. Disclosures Ryan K. Shields, PharmD, MS, Allergan: Advisor/Consultant|Cidara: Advisor/Consultant|Entasis: Advisor/Consultant|GSK: Advisor/Consultant|Melinta: Advisor/Consultant|Melinta: Grant/Research Support|Menarini: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Roche: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Utility: Advisor/Consultant|Venatorx: Advisor/Consultant|Venatorx: Grant/Research Support

Rationale behind phosphate therapy to modulate the gut microbiome and protect against surgery-related infection

Despite major advances in infection control and the ever-increasing use of broader-spectrum antibiotics in surgery, postoperative infections continue to occur under the best of care and in the best institutions. Postoperative infections, also termed surgical site infections (SSIs), can range from superficial wound infections to deep organ space infections. SSIs can be superficial and only require medical treatment (i.e. antibiotics), whereas others such as deep organ space infections resulting from an anastomotic leak can require multiple surgeries leading to sepsis and occasionally shock and death. Many if not most stakeholders in the field including surgeons, infectious disease specialists, infection control nurses, etc., in general, advocate the use of prophylactic antibiotics and the enforcement of greater levels of sterility, reasoning that all postoperative infections must arise from some type of direct contamination event. In this article, the alternative view is presented that today, in the era of mandated asepsis protocols, enhanced recovery programs, and enforcement of prophylactic antibiotics in all cases, many if not most postoperative infections and SSIs occur from pathogens endogenous to the patient and not from sources exogenous to the patient. It is also suggested that applying broader antibiotic coverage in elective surgery is neither an evolutionarily stable strategy nor inexorable in the context of emerging knowledge in the field of gut ecology. Here this concept is reviewed and the rationale behind using agents that preserve the gut microbiome and attenuate pathogen virulence in lieu of applying broader-spectrum antibiotics and greater levels of sterility.

Association of a sepsis initiative on broad spectrum antibiotic use and outcomes in an ED population

IntroductionSepsis identification and treatment is a priority for emergency department (ED) providers and payors alike. However, aggressive metrics aimed at improving sepsis care could have unintended consequences for patients who do not have sepsis. MethodsAll ED patient visits for a one month period before and after a quality initiative to increase early antibiotic use in septic patients were included. Overall broad spectrum (BS) antibiotic use, admission rates, and mortality were compared in the 2 time periods. A more detailed chart review was performed on those who received BS antibiotics in the before and after cohorts. Patient were excluded for pregnancy, age < 18, COVID-19 infection, hospice patients, left ED against medical advice, and if antibiotics were given for prophylaxis. In BS antibiotic treated patients, we sought to determine mortality, rates of subsequent multidrug resistant (MDR) or Clostridium Difficile (CDiff) infections and rates of non-infected patients receiving BS antibiotics. ResultsThere were 7967 and 7407 ED visits in the pre- and post-implementation periods, respectively. Of those, BS antibiotics were administered in a total of 3.9% pre-implementation and 6.2% post-implementation (p ≤ 0.00001). Admission was more common in the post-implementation period, but overall mortality was unchanged (0.9% pre-implementation and 0.8% post-implementation, p = 0.41). After exclusions, 654 patients treated with BS antibiotics were included in the secondary analyses. Baseline characteristics were similar between the pre-implementation and post-implementation cohorts. There was no difference in the rate of CDiff infection or the proportion of patients receiving BS antibiotics who were not infected, but there was an increase in the post-implementation period in MDR infections after ED BS antibiotics, 0.72% vs. 0.35% of the entire ED cohorts, p = 0.0009. ConclusionsWe found that a QI sepsis initiative was associated with an increase in the proportion of patients who received BS antibiotics in the ED, and a small absolute increase in associated subsequent MDR infections, with no apparent effect on mortality in all ED patients or the subset treated with BS antibiotics. Further research is needed to assess the impact on all patients affected by aggressive sepsis protocols and initiatives, rather than only those with sepsis.

Removal of incorrect penicillin allergy labels in a UK hospital

ObjectivesPenicillin allergy records are common, often incorrect and are associated with broad spectrum antibiotic use. We piloted a pharmacist-led multidisciplinary penicillin allergy de-labelling daily ward round to determine the opportunity for penicillin allergy de-labelling in a UK hospital. MethodsA daily ward round, delivered by antibiotic pharmacists or junior doctors, identified adult medical and surgical patients between 7 November 2022 and 31 January 2023 with a penicillin allergy record that was preventing first-line penicillin use. An allergy history was taken before risk stratifying likelihood of future harm from penicillin re-exposure and an allergy testing method was determined (direct de-label on history alone or after direct drug provocation testing). After successful allergy de-label, the antibiotic was switched to a penicillin antibiotic. ResultsOf 7214 inpatients during the study period, 1133 (15.7%) had a penicillin allergy record. Of 285 allergy histories taken, 105 (36.8%) met high-risk criteria, 45 (15.8%) met low-risk criteria eligible for direct de-label and 73 (25.6%) met criteria eligible for direct drug provocation testing. We were unable to obtain a history for 61 (21.4%) patients. Of 45 low-risk patients eligible for direct de-label, 40 (88.9%) were de-labelled of whom 24 (53.3%) were switched to a penicillin antibiotic. Of 73 patients with a low-risk allergy history eligible for direct drug provocation testing, 16 (21.9%) received direct drug provocation testing, of whom 9 were switched to a penicillin antibiotic. Two direct de-label patients experienced harm (thrush within 5 days and delayed skin reaction after day 5); none of the direct drug provocation testing patients had a reaction by day 5. The switches resulted in reduced alternative antibiotic use by 173 Daily Defined Doses (DDDs). DiscussionPenicillin allergy de-labelling patient pathway delivered by pharmacists and junior doctors was safe and effective and well accepted by patients and the wider clinical teams.

The Efficacy of Flogofilm® in the Treatment of Chronic Bacterial Prostatitis as an Adjuvant to Antibiotic Therapy: A Randomized Prospective Trial.

Bacterial prostatitis (BP) is a common prostatic infection characterized by a bimodal distribution in young and older men, with a prevalence between 5-10% among all cases of prostatitis and a high impact on quality of life. Although the management of bacterial prostatitis involves the use of appropriate spectrum antibiotics, which represent the first choice of treatment, a multimodal approach encompassing antibiotics and nutraceutical products in order to improve the efficacy of chosen antimicrobial regimen is often required. To evaluate the efficacy of Flogofilm® in association with fluoroquinolones in patients with chronic bacterial prostatitis (CBP). Patients diagnosed with prostatitis (positivity to Meares-Stamey Test and symptoms duration > 3 months) at the University of Naples "Federico II", Italy, from July 2021 to December 2021, were included in this study. All patients underwent bacterial cultures and trans-rectal ultrasounds. Patients were randomized into two groups (A and B) receiving antibiotic alone or an association of antibiotics plus Flogofilm® tablets containing Flogomicina® for one month, respectively. The NIH-CPSI and IPSS questionnaires were administered at baseline, four weeks, twelve and twenty-four weeks. A total of 96 (Group A = 47, Group B = 49) patients concluded the study protocol. The mean age was comparable, with a mean age of 34.62 ± 9.04 years for Group A and 35.29 ± 10.32 years for Group B (p = 0.755), and IPSS at the baseline was 8.28 ± 6.33 and 9.88 ± 6.89 (p = 0.256), respectively, while NIH-CPSI at baseline was 21.70 ± 4.38 and 21.67 ± 6.06 (p = 0.959), respectively. At 1, 3 and 6 months, the IPSS score was 6.45 ± 4.8 versus 4.31 ± 4.35 (p = 0.020), 5.32 ± 4.63 versus 3.20 ± 3.05 (p = 0.042) and 4.91 ± 4.47 versus 2.63 ± 3.28 (p = 0.005) for Groups A and B, respectively. Similarly, the NIH-CPSI total score at 1, 3 and 6 months was 16.15 ± 3.31 versus 13.10 ± 5.03 (p < 0.0001), 13.47 ± 3.07 versus 9.65 ± 4.23 (p < 0.0001) and 9.83 ± 2.53 versus 5.51 ± 2.84 (p < 0.0001), respectively. Flogofilm®, associated with fluoroquinolones, demonstrate a significant improvement in pain, urinary symptoms and quality of life in patients affected by chronic bacterial prostatitis in both IPSS and NIH-CPSI scores compared with fluoroquinolones alone.

A Quality Improvement Intervention to Enhance Cephalosporin Utilization for Surgical Prophylaxis in Reported Penicillin Allergy

Patient reported penicillin allergy is associated with higher rates of surgical site infections and alternative broad spectrum antibiotic use for surgical prophylaxis. This study evaluated a quality improvement intervention to increase cephalosporin use in perioperative patients with reported penicillin allergy in a hospital with a strong antimicrobial stewardship program.

566. The Impact of a Clinical Practice Guideline and Educational Interventions on the Management of Children Hospitalized with Uncomplicated Community Acquired Pneumonia

Abstract Background The 2011 guidelines for management of pediatric uncomplicated community acquired pneumonia (CAP) recommend the use of ampicillin or penicillin first line. We sought to evaluate improvement in adherence to these guidelines through antimicrobial stewardship interventions at a single institution to minimize unnecessary broad antimicrobials. Methods A retrospective chart review was conducted of admitted patients aged 2 months - 21 years old with uncomplicated CAP. The pre-intervention phase was September 1, 2019-February 29, 2020 and the post-intervention phase included September 1-February 28 of 2021 and 2022. Antimicrobial stewardship interventions included the incorporation of clinical practice guidelines (CPG) into a new institutional CAP pathway (approved in June 2020) and subsequent education to ordering providers in the spring of 2020. Patients with complicated pneumonia or with comorbidities including sickle cell disease, chronic lung disease, neurologic conditions, congenital heart disease or patients who were immunocompromised were excluded. The prescribing patterns of specific physicians were recorded and adherence to CPG recommendations were assessed. The primary endpoint was to measure the reduction of broad spectrum antibiotics (vancomycin, clindamycin, ceftriaxone, levofloxacin and cefdinir) to narrow spectrum antibiotics (ampicillin, amoxicillin, and amoxicillin-clavulanate). Results A total of 114 patients were included in the study; 72 pre-intervention and 42 post-intervention. Mean age was 5.4 years pre- and 6.5 years post-intervention. A significant reduction in broad spectrum antibiotic use was noted in the ED (p=&amp;lt; 0.0001), during the first 24 hours of admission (p=0.0034) and for discharge antibiotics (p=0.0003) (Figures 1-3) between the pre- and post-intervention groups. Guideline adherence was 78.5%. No change in length of stay or treatment failure were observed. Antibiotic Prescriptions in the Emergency Department After the implementation of the CPG guideline there was a 17% reduction in the number of times a combination of antibiotics were used, a 7.2% reduction of broad spectrum antibiotics and a 24% increase in the utilization of narrow spectrum antibiotics, p-value= &amp;lt;0.0001. Antibiotic Utilization 24 hours After Hospital Admission After the implementation of the CPG guideline there was a 20% reduction in the number of times a broad spectrum antibiotic was prescribed, p-value =0.0034. Discharge Antibiotic Prescriptions After the implementation of the CPG guideline there was a 18% reduction of broad spectrum antibiotics and a 34% increase in the utilization of narrow spectrum antibiotics, p=0.0003. Conclusion The CPG and educational interventions had a positive impact on the antibiotic management of children hospitalized, with an overall 4.7% reduction of broad spectrum antibiotics and a 28% increase in the utilization of narrow spectrum antibiotics. Continued education may improve CPG adherence. Disclosures All Authors: No reported disclosures.

294. Risk factors of COVID-19 associated pulmonary aspergillosis in a high endemic setting and development of a bedside clinical risk prediction score.

Abstract Background India has a high burden of invasive fungal infections. Although invasive aspergillosis was also reported during the COVID-19 pandemic, the real world data on the risk factors and outcome of CAPA are limited. Our aim is to determine risk factors and clinical outcomes of CAPA and develop a prediction model for patient stratification. Methods A retrospective, case-control study was conducted at a 1300-bedded South Indian tertiary care academic centre from June 1st, 2020 to May 31st, 2021. CAPA cases were defined by 2020 ECMM/ISHAM consensus criteria as possible, probable, and proven infection. Age and admission period matched control group with COVID-19 but without aspergillosis was selected in a 1:1 ratio. A risk scoring stratification for CAPA was developed based on the significant CAPA risk factors using logistic regression model. Figure 1:Receiving operating characteristic curve of CAPA incidence score for predicting CAPA in the study cohort Results 95 CAPA cases, of which 75(79%) were probable and 20(21%) possible, were diagnosed during the study period. 84(88.4%) patients had moderate to severe COVID-19, and 75(78.9%) were treated with steroids, most commonly dexamethasone (Table 1). The time from COVID-19 diagnosis to CAPA was 13 days (IQR 12). 40(42.1%) of patients were on mechanical ventilation at CAPA diagnosis. Outcome measures (MV, NIV and hospital/ICU stay) were significantly higher in CAPA patients compared to controls(Table 2). Neutropenia, use of steroids, broad spectrum antibiotic use, fluconazole prophylaxis and absence of co-infecting pathogen were found to be significant factors associated with CAPA(p&amp;lt; 0.05) (Table 3). An optimal risk score of ≥10.00 predicted CAPA with a sensitivity of 84.2% and a specificity of 59% with an area under the curve of 0.77 (PPV=67.23%, NPV=78.87%)(Fig 1). 75(78.9%) patients had positive serum aspergillus galactomannan with an average value of 1.89±1.65. 28-day (41.1% vs 33.7%, p=0.13) and 6-week all cause-mortality (48.4% vs 37.9%, p=0.07) were higher, but not statistically significant, for CAPA. Table 1:Baseline characteristics and risk factorsTable 2:Primary and secondary outcomesTable 3:CAPA incidence scoring table Significant univariate variables were included in the multivariate logistic regression model and predicted probabilities based on the beta co-efficients of the significant variables in the model were transformed to generate CAPA incidence score for patients. Conclusion Risk factors of CAPA in Indian were similar to those reported previously in other countries. CAPA can be seen in severe COVID-19 patients who are not mechanically ventilated. A CAPA risk scoring system, that needs external validation, is a simple and feasible tool that could be useful in stratification of patients suspected of CAPA. Disclosures All Authors: No reported disclosures.

UTILIZATION OF A HOSPITALIST DRIVEN PENICILLIN SKIN TESTING PROTOCOL TO PROMOTE ANTIBIOTIC STEWARDSHIP

<h3>Introduction</h3> Antibiotic resistance is an increasing problem throughout the world. Inappropriate labeling of penicillin allergies results in suboptimal antibiotic selection for patients. Penicillin skin testing is a valuable tool for facilitating a switch to beta-lactam antibiotics. <h3>Methods</h3> A retrospective analysis of all patients with a documented history of penicillin allergy were included in the study from March 2017 to May 2019; a total of 128 patients were included. Analysis involved nature of penicillin allergy and results of penicillin skin test. Benzylpenicilloyl polylysine (PRE-PEN®) tested major determinant, and diluted penicillin G tested minor determinant. The primary outcome of the study is the rate of antibiotic deescalation, and secondary outcome is a comparison of the duration of non beta-lactam therapy in appropriately re-labeled versus non re-labeled subjects (student t-test). <h3>Results</h3> 12 of 128 patients (9.4%) had a negative histamine test and were labeled indeterminate. Of the remaining 116 patients, 111 had a negative test (95.7%) and 5 (4.3%) had a positive test to PRE-PEN ® or dilute penicillin G. 78 of the 111 negative (70.3%) were switched to a narrower spectrum-based antibiotic, and subsequently did not experience allergic reaction. There was a significantly decreased use of vancomycin, aztreonam, carbapenem, fluoroquinolone and clindamycin. There was no significant difference in duration of non beta-lactam therapy in appropriately re-labeled versus non re-labeled subjects (3.6 days vs. 4.25 days; p=0.35). <h3>Conclusion</h3> Our protocol has demonstrated that a penicillin skin testing protocol can substantially reduce broad spectrum antibiotic use and increase antibiotic stewardship.

Evaluation of the effectiveness of an automated sepsis predictive tool on patient outcomes.

To evaluate the effectiveness of a multidisciplinary, hospital-wide program as part of an electronic sepsis alert tool. We used data from 15 hospitals about adult patients with severe sepsis or septic shock. Nine intervention hospitals implemented an Epic sepsis prediction tool, education, and standardized order sets (six control hospitals did not). A difference-in-difference approach evaluated their effectiveness: 1) pre-implementation period (January 1, 2016-November 15, 2018) and 2) implementation period (November 16, 2018-June 30, 2019). Outcomes included mortality, receipt of the SEP-1 bundle of care, broad spectrum antibiotic use, ICU stay, and length of stay of 6926 patients. The difference of 6.7 percentage points between the intervention and control groups in SEP-1 bundle completion was not statistically significant (p = 0.105). The increase over time for antibiotic administration ≤1 h of time zero was not larger for hospitals in the intervention group (11.7%) compared to the control-group (7.6%, p = 0.084). Differences among hospitals in both groups were not statistically different for mortality (p = 0.174), ICU stays (p = 0.174), and length of stay (p = 0.652) from pre- to implementation period. The intervention to facilitate timely sepsis care did not improve patient outcomes among those with severe sepsis or septic shock.

MO116: Vitamin C Nephrotoxicity in a COVID-19 Patient: A Case Report

BACKGROUND AND AIMSDuring the time of the COVID-19 pandemic, multiple treatment options have been investigated, even though their efficacy and secondary effects remain insufficiently known.We report the case of a vitamin C induced oxalate nephropathy in a COVID-19 patient with preexisting chronic kidney disease (CKD) resulting in irreversible acute renal failure.Vitamin C, also known as ascorbic acid, has been used as an anti-inflammatory therapy for COVID-19, but review of the literature shows similar cases of acute kidney injury (AKI), raising concern.METHODWe report the case of a 73-year-old Caucasian woman admitted for hyperthermia and digestive disorders. She had recently started a first-line chemotherapy for multiple myeloma with partial response. She also displayed preexisting stage 4 CKD (eGFR 18.50 mL/min/1.73 m² using CKD-EPI) of unknown aetiology.She was tested positive for SARS-CoV2 by nasopharyngeal swab and soon transferred to the intensive care unit. She received intravenous corticosteroids using dexamethasone 6 g/24 h for 10 days and a piperacillin + tazobactam probabilistic antibiotherapy. She also received high doses (15 g/24 h) of vitamin C for three consecutive days. No monoclonal antibodies were prescribed due to a previous vaccination with a positive serology upon admission.Although the patient recovered from respiratory tract infection, her kidney function progressively deteriorated with serum creatinine levels rising up to 8.06 g/dL, leading to her admission in our nephrology department. The patient was initially treated with high doses of diuretics for anasarca and an abdominal CT excluded urinary tract obstruction with normal kidney size and aspect. Urinary analysis showed protein to creatinine (p/c) ratio of 1348 g/g, and presence of urinary light chains. Her monoclonal spike was measured at 2.3 g/L and her kappa/lambda fraction was 1.74.Intermittent haemodialysis was initiated, and a kidney biopsy was performed.RESULTSHistology revealed hundreds of intratubular calcium oxalate crystals, with severe and diffuse acute tubular necrosis and interstitial edema. There was no amyloidosis, no sign of active glomerular disease and no interstitial fibrosis. Immunofluorescence (IgA, IgG, IgM, C1Q, C3, kappa and lambda) was negative. We concluded to oxalate nephropathy.After a 2-month follow-up, the patient remains dialysis dependent.Vitamin C is a precursor of oxalate and has been shown to cause secondary oxaluria, particularly with high-dose regimens in patients with altered renal function. Given the histological findings evocative of acute oxalate nephropathy, the accountability of high doses of vitamin C should be considered.No other cause of hyperoxaluria was identified in our patient beside broad spectrum antibiotic use, which could decrease intestinal bacterial oxalate degradation. In particular, there was no malabsorptionThe limitation of our report is the unknown cause of preexisting CKD; therefore, we cannot rule out preexisting hyperoxaluria. Also, no dosage of serum vitamin C and oxalate levels were performed during follow-up. Finally, our patient had other possible causes AKI, such as recent SARS-CoV2 infection, or linked to multiple myeloma, but these were considered unlikely given the proper haematological response to treatment and non-evocative biopsy.The rationale for vitamin C use in COVID-19 is based on in vitro studies showing its antioxidant, anti-inflammatory, anticoagulant and immune modulatory properties. There lack large clinical studies, and the literature shows conflicting results. Multiple cases of acute oxalate nephropathy were described.CONCLUSIONVitamin C is an anti-inflammatory treatment used in COVID-19 that can lead to secondary hyperoxaluria with significant and irreversible AKI. Due to the severity of AKI in patients with preexisting CKD, we believe renal function should be considered before using high doses of vitamin C.Larger controlled trials are needed both to establish the clinical benefit of vitamin C and further describe its potential nephrotoxicity.

Impact of antibiotic susceptibility reporting on broad spectrum antibiotic use in serratia and morganella bacteremia

To minimize broad-spectrum antibiotic use, our microbiology laboratory changed antibiotic susceptibility reporting for AmpC-beta-lactamase producing Serratia marcescens and Morganella morganii in blood cultures to include results of narrow spectrum 3rd generation cephalosporins. We assessed the impact of this change on broad-spectrum antibiotic use and clinical outcomes. All adult patients with Serratia marcescens or Morganella morganii in blood culture 2 years pre- and post-change of susceptibility reporting were retrospectively reviewed. Exclusion: more than one pathogen isolated in their blood culture, did not receive antibiotics or died within 48 hours of positive blood culture. Outcomes: Rates of broad-spectrum antibiotic use, in-hospital mortality, clinical response and microbiologic success. There were 30 patients pre-change and 46 patients post-change of reporting. Cefepime use (broad-spectrum) decreased from 46.7% to 6.5% (p < 0.001) and 3rd generation cephalosporin (narrow-spectrum) use increased (3.3% vs 34.8%, p = 0.0013) in the post-change cohort. This demonstrates the potential role of selective susceptibility reporting in antimicrobial stewardship.

P13 Development of a consult and antimicrobial stewardship service in Manchester Foundation Trust

ObjectivesTo prospectively audit the first year of the North Manchester infectious diseases AMS and Consult service June 2020 to June 2021 to: (i) characterize the number of patients who had antibiotic treatment narrowed, duration reduced and/or switch to oral options; (ii) assess documentation of indication and duration of antibiotic prescriptions; (iii) determine whether or not the appropriate microbiological specimens have been performed and with the lab; (iv) identify the impact on antibiotic consumption measured in defined daily dose (DDDs); and (v) establish whether base teams act on the advice given by the Consult/AMS team (data over a 6 week period).MethodsOn weekdays an electronic prescribing list of all patients prescribed piperacillin/tazobactam, meropenem and ciprofloxacin was generated, and the consults team performed either a bedside or notes review. Data was collected prospectively on 730 patients on which infection was treated, which specialty managed the patient, microbiology samples sent, duration and indication of treatment documentation, and advice given by consults team. Data was then collected over a further 6 weeks looking at whether the base specialty carried out the advice of the AMS team.ResultsThe main indication for broad spectrum antibiotic use was urinary tract infection (151/720) and hospital acquired pneumonia (104/720). Poor documentation of antimicrobial indication and duration was observed across all specialties (277/720). Just over 50% of appropriate microbiology samples were sent (422/726). For 42% of cases (311/730), colleagues were advised to stop or reduce antibiotic duration. In 30% of cases (220/730), narrowing of antibiotic spectrum was advised. Thirty percent (219/730) were advised on IV to oral switch. There was a modest reduction in antimicrobial consumption in some specialties comparing the year prior to the introduction of the service 2019–20 to 2020–21; 17.4% reduction respiratory (7810/9137), 0.2% increase in medicine (272698/267351) and 2.1% surgery (68722/67309). In 81 patients reviewed to look at outcomes over 6 weeks, 88% of Consult/AMS team advice was actioned by the lead specialties involved in the patients’ care.Conclusions(i) There is a substantial need for an AMS service within the hospital. (ii) Outcome data shows the ward teams engage with the service and most follow advice. (iii) The service contributed to limiting inappropriate prescribing during the COVID-19 pandemic. There was a modest rise in hospital-wide consumption. (iv) The AMS service needs to be available to provide patient equity across Manchester Foundation Trust, fostering a city-wide AMS strategy that encompasses education, guidelines, audit and quality improvement.

Intra Ventricular Colistin in Neonatal Brain Abscess Management: A Case of Multiple Brain Abscesses

Neonatal Brain abscess is a rare sever neonatal infection requiring careful medical and neurosurgical intervention strategies to reduce morbidity and mortality rates. Gram-negative bacterial agents are the most common pathogens involved in brain abscesses of neonates. The use of wide spectrum antibiotics in combination with neurosurgical drainage of abscesses larger than 2.5 cm is the mainstay of treatment. Colistin is a polymyxin antibiotic used to treat bacterial infections caused by susceptible gram-negative bacteria but with a limited penetration in blood brain barrier. However, there is limited data on using intraventricular Colistin in neonatal intracranial infections. A 12-day-old male neonate with multiple brain abscesses in frontal and parietal lobes is presented. The abscesses were successfully managed with a combination of intravenous antimicrobial agents, intraventricular Colistin and concurrent administration of Interferon-ɣ. Subsequently, he developed ventriculomegaly which was successfully managed by endoscopic third ventriculostomy. He had an acceptable neurologic outcome. Due to reduced penetration of colistin in blood brain barrier, use of intraventricular Colistin in combination with its intravenous form can be beneficial in management of neonatal brain abscesses. Concurrent administration of Interferon-ɣ may improve the treatment process and outcome given that reduced secretion of this agent by neonatal T lymphocytes may contribute to a partial immunodeficiency state at this period of life.

13. INSPIRE-ASP Pneumonia Trial: A 59 Hospital Cluster Randomized Evaluation of INtelligent Stewardship Prompts to Improve Real-time Empiric Antibiotic Selection versus Routine Antibiotic Selection Practices for Patients with Pneumonia

13. INSPIRE-ASP Pneumonia Trial: A 59 Hospital Cluster Randomized Evaluation of INtelligent Stewardship Prompts to Improve Real-time Empiric Antibiotic Selection versus Routine Antibiotic Selection Practices for Patients with Pneumonia

653. Direct Identification of Microorganisms in Positive Blood Cultures by the BioFire® FilmArray® Blood Culture Identification Panel Leads to Faster Optimal Antibiotic Therapy: A Before–After Study

BackgroundRapid pathogen identification from positive blood cultures may help optimize empiric antibiotic therapy quickly by reducing unnecessary broad spectrum antibiotic use and may improve patient outcomes. The BioFire® FilmArray® Blood Culture Identification Panel 1 (BF-FA-BCIP) identifies 24 pathogens directly from positive blood cultures without subculture. 3 resistance genes are included. We aimed to compare the time to optimal antibiotic therapy between BF-FA-BCIP and conventional identification.MethodsWe performed a single-center retrospective case-control before-after study of 386 cases (November 2018 to October 2019) with BF-FA-BCIP compared to 414 controls (August 2017 to July 2018) with conventional identification. The primary study endpoint was the time from blood sampling to implementation of optimal antimicrobial therapy. Secondary endpoints were time to effective therapy, length of hospital stay, and in-hospital and 30-day mortality. Outcomes were assessed using cause-specific Cox Proportional Hazard models and logistic regressions.ResultsWe included 800 patients with comparable baseline characteristics. Main sources of blood stream infection (BSI) were urinary tract infection and intra-abdominal infection (19.2% vs. 22.0% and 16.8% vs. 15.7% for case and control groups, respectively). Overall, 212 positive blood cultures were considered as contaminations. Identification results were available after a median of 21.9 hours by the BF-FA-BCIP and 44.3 hours by the conventional method. Patients with BF-FA-BCIP received the optimal therapy after a median of 25.5 hours (95%CI 21.0 - 31.2) as compared to 45.7 hours (95%CI 37.7 - 51.2) in the control group (Figure 1). We found no effect of the identification method on secondary outcomes.Kaplan-Meier curve representing the probability of implementing the optimal therapy at any given time according to the identification method (Standard vs. BF-FA-BCIP). Shaded ribbons represent the 95 % confidence interval (CI). The vertical dashes represent censored data. The vertical dotted lines represent the median time, i.e. the time at which 50 % of the patients obtained the optimal therapy, for the two methods. Median (95 % CI) time to optimal therapy is 45.7 (37.7 - 51.4) hours with the Standard method and 25.5 (21.0- 31.2) hours with Biofire. The tables below the curves present the numbers expecting optimal therapy according to the bacteria identification method, as well as the number of censored data in parenthesis. Panel A shows data from 0 to 900 hours. Panel B shows the data from 0 to 90 hours to better visualize how the probability to implement optimal therapy varies in the first 72 hours.ConclusionIn conclusion, rapid pathogen identification by BF-FA-BCIP was associated with an almost 24h earlier initiation of the optimal antibiotic therapy in BSI. However, the overall benefit for individual patients seems to be limited. Future studies should assess the cost-effectiveness and impact on the prevention of antibiotic resistance using this diagnostic approach.Disclosures All Authors: No reported disclosures

42. INSPIRE-ASP UTI Trial: A 59 Hospital Cluster Randomized Evaluation of INtelligent Stewardship Prompts to Improve Real-time Empiric Antibiotic Selection versus Routine Antibiotic Selection Practices for Patients with Urinary Tract Infection (UTI)

42. INSPIRE-ASP UTI Trial: A 59 Hospital Cluster Randomized Evaluation of INtelligent Stewardship Prompts to Improve Real-time Empiric Antibiotic Selection versus Routine Antibiotic Selection Practices for Patients with Urinary Tract Infection (UTI)