Definitive Antimicrobial Therapy Research Articles

Antibiotic definitive treatment in ventilator associated pneumonia caused by AmpC-producing Enterobacterales in critically ill patients: a prospective multicenter observational study

BackgroundVentilator associated pneumonia (VAP) due to wild-type AmpC-producing Enterobacterales (wtAE) is frequent in intensive care unit (ICU) patients. Despite a low level of evidence, definitive antimicrobial therapy (AMT) with third generation cephalosporins (3GCs) or piperacillin is discouraged.MethodsObservational prospective study including consecutive wtAE VAP patients in 20 French ICUs. The primary objective was to assess the association of the choice of definitive AMT, i.e. piperacillin ± tazobactam (PTZ), 3GCs or other molecule (4GCs, carbapenems, quinolones, cotrimoxazole; control group), with treatment success at day-7. Recurrence of infection was collected as a secondary outcome, and analyzed accounting for the competing risk of death.ResultsFrom February 2021 to June 2022, 274 patients were included. Enterobacter cloacae was the most prevalent specie (31%). Seventy-eight patients (28%) had PTZ as definitive AMT while 44 (16%) had 3GCs and 152 (56%) were classified in the control group. Day-7 success rate was similar between the 3 groups (74% vs. 73% vs. 68% respectively, p = 0.814). Recurrence probability at day-28 was 31% (95% CI 21–42), 40% (95% CI 26–55) and 21% (95% CI 15–28) for PTZ, 3GCs and control groups (p = 0.020). In multivariable analysis, choice of definitive AMT was not associated with clinical success, but definitive AMT with 3GCs was associated with recurrence at day-28 [csHR(95%CI) 10.9 (1.92–61.91)].ConclusionChoice of definitive antimicrobial therapy was not associated with treatment success at day 7. However, recurrence of pneumonia at day-28 was higher in patients treated with third generation cephalosporins with no differences in mortality or mechanical ventilation duration.

2789. Cefepime Versus Non-Cefepime/Non-Carbapenem Therapy for Blood Stream Infections Caused by Non-ESBL-Producing Serratia Marcescens: A Subgroup Analysis of The Carbapenem-Serratia Multicenter Retrospective Cohort Study

Abstract Background Serratia Marcescens causes serious infections. Carbapenems were prescribed due to the bacterium’s ability to develop inducible AmpC-mediated resistance. Recent IDSA guidance recommends ceftriaxone and in high-burden cases, cefepime. Evidence on the role of cefepime in the treatment of Serratia bacteremia is scarce. We aim to evaluate the outcomes of patients who received cefepime-containing empiric and/or definitive therapy (CFCT) to those receiving non-cefepime therapy (NCFCT). Methods This is a sub-analysis of a retrospective study of 7 Massachusetts acute care hospitals from January 1, 2015, to October 31, 2022. We included hospitalized adults (≥18 years) with Serratia Marcescens bacteremia. IRB approval was obtained. Demographics, clinical course characteristics, and choice of antibiotic therapy were collected. Primary outcome was 30-day mortality, and secondary outcome was composite antimicrobial failure (see Definitions in Table 1). Chi Square and Mann-Whitney U tests were computed using SPSS statistical package. Results The original Carbapenem-Serratia study had 73 out of 128 patients who met the inclusion criteria (Figure 1). The non-carbapenem group (n=56) was further studied for the purpose of this subanalysis and was divided into CFCT (n=15) and NCFCT (n=41). The two subgroups were similar in baseline comorbidities, severity measures, and sources of bacteremia (Table 1). Neither 30-day mortality nor the composite outcome of antimicrobial failure were significantly different with relative risks of 0.94 (95% CI 0.16 to 5.3, P=0.948) and 1.21 (95% CI 0.27 to 5.4, P=0.800), respectively. Study exclusion flow-chart with subanlaysis. ESBL phenotypically defined by ceftriaxone resistance (MIC <1). Characteristics and outcomes of patient with Serratia bacteremia treated with a cefepime versus non-cefepime nor carbapenem therapy regimen. * Immunocompromised patients are those receiving immunosuppressants, chemotherapy, or transplants, having HIV with CD4+ T cell count <200 cells/mm3, neutropenia with ANC < 500 cells/mm3, or corticosteroid use with prednisone or equivalent >10 mg for ≥ 14 days. † Hospital-acquired bacteremia is diagnosed when a positive blood culture obtained from patients hospitalized for 48 hours or longer. Healthcare-associated bacteremia was defined as a positive blood culture is obtained within 48 hours of hospital admission and the patient fulfills specific pre-defined criteria utilized in prior studies. Community-acquired bacteremia refers to positive a blood culture obtained within 48 hours after hospital admission in patients who do not fit the criteria for healthcare-associated infections. ‡ Deep seated complicated infection included Infective endocarditis, septic arthritis, osteomyelitis, or epidural abscess § Empiric antibiotic therapy: Antibiotics administered before antimicrobial susceptibility testing (AST) results, with a minimum 48-hour of uninterrupted duration and appropriate dosing. || Definitive antibiotic therapy (i.e., antibiotics administered after the AST results, also with a minimum of 48-hour duration). ¶ Duration of total definitive antibiotic therapy was counted from day of AST results until last day of definitive antimicrobial therapy. # Microbiological failure, microbiological relapse, in- hospital mortality, 30-day mortality, infection-related hospital readmission, or recurrent Serratia bateremia within 30 days. Microbiological failure refers to the growth of Serratia after 48 hours of definitive antibiotic therapy, while microbiological relapse is the regrowth of Serratia after a negative blood culture (Kunz Coyne et al., 2023). Note: Two patients had recurrence of Serratia bacteremia within 30 days, neither were resistant to third generation cephalosporins. Δ Infection-related re-admission was defined when a patient is readmitted not solely for a procedure or surgery, and they experience fever, worsening leukocytosis, or required escalation of antimicrobial therapy from the definitive therapy of the index admission. Conclusion Averting cefepime in the antimicrobial therapy of Serratia bacteremia is not associated with a significant increase in 30-day mortality or the composite outcome of antimicrobial failure. When applicable, a narrower beta-lactam therapy such as ceftriaxone may be appropriate. Limitations include a small sample size, with higher risk for type II error, and overlap in definitive antibiotic therapy. Further prospective studies are needed to confirm these findings, especially in patients with deep-seated infections. Disclosures All Authors: No reported disclosures

IWGDF/IDSA Guidelines on the Diagnosis and Treatment of Diabetes-related Foot Infections (IWGDF/IDSA 2023).

The International Working Group on the Diabetic Foot (IWGDF) has published evidence-based guidelines on the management and prevention of diabetes-related foot diseases since 1999. The present guideline is an update of the 2019 IWGDF guideline on the diagnosis and management of foot infections in persons with diabetes mellitus. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was used for the development of this guideline. This was structured around identifying clinically relevant questions in the P(A)ICO format, determining patient-important outcomes, systematically reviewing the evidence, assessing the certainty of the evidence, and finally moving from evidence to the recommendation. This guideline was developed for healthcare professionals involved in diabetes-related foot care to inform clinical care around patient-important outcomes. Two systematic reviews from 2019 were updated to inform this guideline, and a total of 149 studies (62 new) meeting inclusion criteria were identified from the updated search and incorporated in this guideline. Updated recommendations are derived from these systematic reviews, and best practice statements made where evidence was not available. Evidence was weighed in light of benefits and harms to arrive at a recommendation. The certainty of the evidence for some recommendations was modified in this update with a more refined application of the GRADE framework centred around patient important outcomes. This is highlighted in the rationale section of this update. A note is also made where the newly identified evidence did not alter the strength or certainty of evidence for previous recommendations. The recommendations presented here continue to cover various aspects of diagnosing soft tissue and bone infections, including the classification scheme for diagnosing infection and its severity. Guidance on how to collect microbiological samples, and how to process them to identify causative pathogens, is also outlined. Finally, we present the approach to treating foot infections in persons with diabetes, including selecting appropriate empiric and definitive antimicrobial therapy for soft tissue and bone infections; when and how to approach surgical treatment; and which adjunctive treatments may or may not affect the infectious outcomes of diabetes-related foot problems. We believe that following these recommendations will help healthcare professionals provide better care for persons with diabetes and foot infections, prevent the number of foot and limb amputations, and reduce the patient and healthcare burden of diabetes-related foot disease.

IWGDF/IDSA guidelines on the diagnosis and treatment of diabetes-related foot infections (IWGDF/IDSA 2023).

The International Working Group on the Diabetic Foot (IWGDF) has published evidence-based guidelines on the management and prevention of diabetes-related foot diseases since 1999. The present guideline is an update of the 2019 IWGDF guideline on the diagnosis and management of foot infections in persons with diabetes mellitus. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was used for the development of this guideline. This was structured around identifying clinically relevant questions in the P(A)ICO format, determining patient-important outcomes, systematically reviewing the evidence, assessing the certainty of the evidence, and finally moving from evidence to the recommendation. This guideline was developed for healthcare professionals involved in diabetes-related foot care to inform clinical care around patient-important outcomes. Two systematic reviews from 2019 were updated to inform this guideline, and a total of 149 studies (62 new) meeting inclusion criteria were identified from the updated search and incorporated in this guideline. Updated recommendations are derived from these systematic reviews, and best practice statements made where evidence was not available. Evidence was weighed in light of benefits and harms to arrive at a recommendation. The certainty of the evidence for some recommendations was modified in this update with a more refined application of the GRADE framework centred around patient important outcomes. This is highlighted in the rationale section of this update. A note is also made where the newly identified evidence did not alter the strength or certainty of evidence for previous recommendations. The recommendations presented here continue to cover various aspects of diagnosing soft tissue and bone infections, including the classification scheme for diagnosing infection and its severity. Guidance on how to collect microbiological samples, and how to process them to identify causative pathogens, is also outlined. Finally, we present the approach to treating foot infections in persons with diabetes, including selecting appropriate empiric and definitive antimicrobial therapy for soft tissue and bone infections; when and how to approach surgical treatment; and which adjunctive treatments may or may not affect the infectious outcomes of diabetes-related foot problems. We believe that following these recommendations will help healthcare professionals provide better care for persons with diabetes and foot infections, prevent the number of foot and limb amputations, and reduce the patient and healthcare burden of diabetes-related foot disease.

1334. Radiographic Features Associated with Increased Microbiology Culture Yields in Pediatric Orbital Cellulitis

Abstract Background Orbital cellulitis is an invasive infection defined by its location posterior to the orbital septum and can result in severe clinical manifestations. Computed tomography (CT) is the recommended imaging modality to assess for extent of disease and the Chandler classification system is used. It has 5 stages (CS): I is preseptal; II has inflammation beyond the orbital septum; III has subperiosteal abscess; IV has orbital abscess; and V has cavernous sinus thrombosis. There is limited data in its association with microbiology culture results. As part of a larger study to capture epidemiological and microbiological trends in pediatric orbital we hypothesize that culture yields and identification of a causative pathogen would increase as CS increases. Methods We performed a retrospective analysis using the US Military Health System database. ICD9/10 codes identified Individuals ≤ 21 years from June 2009 to September 2019 with orbital cellulitis. We excluded ophthalmia neonatorum and any cases without radiographic confirmation of orbital involvement. Demographic data, co-morbid diagnoses, imaging studies, microbiology results, and antibiotics prescribed were collected. CT reports were reviewed, and cases grouped by Chandler stage, (CS II-V). Descriptive statistics and χ 2 tests were used for categorical variables when appropriate. Results 130 cases met the inclusion criteria. 66.9% were male, the median age was 9 years old (IQR 4-17), and 55.4% had a prior diagnosis of sinusitis. 50.7% of cases were classified as CS II, 35.3% as CS III, 13.1% as CS IV, and 0.01% as CS V. Microbiology cultures were positive in 33.8% of cases. There was a significant difference between CS and any culture positivity with p = 0.011 and there was a significant trend between increasing CS and culture positivity with p < 0.003. Staphylococcus aureus and Streptococcus intermedius were the two most commonly identified pathogens, with no significant difference or trend associated with CS. Conclusion Overall, our findings demonstrated microbiology yield being low but increases with radiographic characteristics and CS stage. Identification of causative pathogens could increase the likelihood for tailored definitive antimicrobial therapy in pediatric patients with orbital cellulitis. Disclosures All Authors: No reported disclosures.

1426. Empiric Antimicrobial Prescribing for Urinary Tract Infections in Patients Discharged from the Emergency Department

BackgroundUrinary tract infections (UTIs) are commonly treated infections in the emergency department (ED), accounting for 3 million visits annually and 15% of outpatient antibiotic prescriptions. The purpose of this study was to characterize empiric and definitive antimicrobial therapy for treatment of UTIs in a nationally representative sample of ED patients.MethodsThis was a multicenter, retrospective cohort study utilizing the Emergency Medicine PHARMacy Research NETwork (EMPHARM-NET), a network of 15 geographically diverse EDs. Patients ≥18 years presenting to and discharged home from the ED with primary diagnosis code of cystitis, pyelonephritis, or UTI from 2018-2020 were included. We describe empiric intravenous (IV) and oral antibiotics used for the treatment of UTI in patients seen and discharged from the ED.ResultsOf the 3779 ED patients treated for UTI, most were discharged from the ED (n=2483, 66%). Most patients were female (76.3%) and common comorbidities were hypertension (47.8%) and diabetes (26.5%). Most patients had uncomplicated (39.4%) or complicated (40.9%) cystitis. 1134 (45.6%) had a positive urine culture, most commonly E. coli (63%) and K. pneumoniae (13%). The most common antibiotics administered in the ED were ceftriaxone (19.7%), nitrofurantoin (6.2%), cephalexin (5.8%), and sulfamethoxazole/trimethoprim (SMX/TMP, 4.8%). The most common antibiotics prescribed at discharge where cephalexin (33.9%), nitrofurantoin (20.6%), SMX/TMP (12%), ciprofloxacin (8.2%), and cefdinir (8%). The mean length of treatment was 7.1 days (standard deviation 2.5 days). Overall, 454 patients returned to the ED within 30 days. The odds of returning to the ED within 30 days was higher in those that did not have appropriate empiric antibiotics based on susceptibilities (OR 1.37, 95% confidence interval 1.06, 1.78).ConclusionThis multicenter, retrospective cohort study describes ED patients discharged from the ED after UTI diagnosis. Patients presented most commonly for cystitis. Nearly half of discharged patients were culture positive. Antimicrobial selection varied; IV ceftriaxone and oral cephalexin were most commonly empirically utilized to treated patients with UTI. Inappropriate antimicrobial selection increased odds of a return ED visit within 30 days. Disclosures Megan A. Rech, PharmD, MS, BCCCP, FCCM, Spero (Research Grant or Support) Brett Faine, PharmD, Spero Therapeutics (Research Grant or Support) David A. Talan, MD, AbbVie (Consultant)GSK (Consultant)SPERO Therapeutics (Grant/Research Support)

90. Impact of Discrepant Rapid Diagnostic Test (RDT) Results on Antimicrobial Stewardship Program (ASP) Interventions in Patients with Bloodstream Infections (BSI) due to Gram-Negative Bacilli (GNB)

BackgroundImplementation of the Accelerate PhenoTM Gram-negative platform (AXDX) paired with ASP intervention projects to improve time to definitive institutional-preferred antimicrobial therapy (IPT). However, few data describe the impact of discrepant RDT results from standard of care (SOC) methods on antimicrobial prescribing. Here we evaluate the prescribing outcomes for discrepant results following the first year of AXDX + ASP implementation.MethodsConsecutive, non-duplicate blood cultures for adult inpatients with GNB BSI following combined RDT + ASP intervention were included (July 2018 – July 2019). AXDX results were emailed to the ASP in real time then released into the EMR upon ASP review and communication with the treating team. SOC identification (ID; Vitek® MS/Vitek® 2) and antimicrobial susceptibility testing (AST; Trek SensititreTM) followed RDT as the reference standard. IPT was defined as the narrowest susceptible beta-lactam, and a discrepancy was characterized when there was categorical disagreement between RDT and SOC methods. When IPT by AXDX was found to be non-susceptible on SOC, this was characterized as “false susceptible“. Conversely, “false resistance” was assessed when a narrower-spectrum agent was susceptible by SOC. Results were also deemed discrepant when the AXDX provided no/incorrect ID for on-panel organisms, no AST, or a polymicrobial specimen was missed.ResultsSixty-nine of 250 patients (28%) had a discrepancy in organism ID or AST: false resistance (9%), false susceptible (5%), no AST (5%), no ID (4%), incorrect ID (2%), and missed polymicrobial (2%). A prescribing impact occurred in 55% of cases (Table 1), where unnecessarily broad therapy was continued most often. Erroneous escalation (7%) and de-escalation to inactive therapy (7%) occurred less frequently. In-hospital mortality occurred in 4 cases, none of which followed an inappropriate transition to inactive therapy. ConclusionThough the AXDX platform provides rapid ID and AST results, close coordination with Clinical Microbiology and continued ASP follow up are needed to optimize therapy. Although uncommon, the potential for erroneous ASP recommendations to de-escalate to inactive therapy following AXDX results warrants further investigation.DisclosuresAmy J. Mathers, MD, D(ABMM), Accelerate Diagnostics (Consultant)

Guidelines on the diagnosis and treatment of foot infection in persons with diabetes (IWGDF 2019 update).

The International Working Group on the Diabetic Foot (IWGDF) has published evidence-based guidelines on the prevention and management of diabetic foot disease since 1999. This guideline is on the diagnosis and treatment of foot infection in persons with diabetes and updates the 2015 IWGDF infection guideline. On the basis of patient, intervention, comparison, outcomes (PICOs) developed by the infection committee, in conjunction with internal and external reviewers and consultants, and on systematic reviews the committee conducted on the diagnosis of infection (new) and treatment of infection (updated from 2015), we offer 27 recommendations. These cover various aspects of diagnosing soft tissue and bone infection, including the classification scheme for diagnosing infection and its severity. Of note, we have updated this scheme for the first time since we developed it 15 years ago. We also review the microbiology of diabetic foot infections, including how to collect samples and to process them to identify causative pathogens. Finally, we discuss the approach to treating diabetic foot infections, including selecting appropriate empiric and definitive antimicrobial therapy for soft tissue and for bone infections, when and how to approach surgical treatment, and which adjunctive treatments we think are or are not useful for the infectious aspects of diabetic foot problems. For this version of the guideline, we also updated four tables and one figure from the 2016 guideline. We think that following the principles of diagnosing and treating diabetic foot infections outlined in this guideline can help clinicians to provide better care for these patients.

1431. Comparison of Treatment Outcomes with Definitive Antibiotic Therapy and Empiric Antibiotic Therapy in Osteomyelitis

BackgroundDefinitive therapy for osteomyelitis (OM) is thought to be superior to empiric antimicrobial therapy; however, identifying causative pathogens is difficult.MethodsThis retrospective cohort study included patients treated with either definitive or empiric antimicrobial therapy for OM at VA St. Louis HCS between 1 January 2010 and 1 January 2018. Definitive antibiotic therapy was defined as a regimen tailored to susceptibilities of an organism(s) cultured from bone or deep tissue. The primary outcome was treatment failure, defined as a need for unplanned surgical intervention or re-initiation of antibiotic therapy for OM of the same anatomical site within 6-months after initial therapy was discontinued. Secondary outcomes included the incidence of acute kidney injury (AKI), Clostridium difficile-associated diarrhea (CDAD), and thrombocytopenia. Surgical intervention as part of initial therapy, presence of peripheral vascular disease (PVD), creatinine clearance < 50 mL/minute at initiation of therapy, receiving antibiotics at an extended care facility, age > 60 years, and receiving definitive antibiotics were included in a univariate analysis with variables with a P < 0.2 included in a multivariate logistic regression.ResultsThere were 301 patients included; 179 in the definitive therapy group and 122 in the empiric therapy group. Baseline characteristics were similar among groups; however, more patients receiving definitive therapy had a bone biopsy compared with those treated with empiric therapy (58.1% (104/179) vs. 36.8% (45/122); P < 0.05). 33 percent (60/179) of patient treated with definitive therapy failed compared with 45% (55/122) treated with empiric therapy (P = 0.109). No significant differences were observed in secondary outcomes; however non-CDAD diarrhea occurred more in the empiric therapy group than definitive therapy group (3.9% (7/179) vs. 8.2% (10/122); P > 0.05). Receiving definitive therapy (OR 1.43, CI 0.89–2.313; P = 0.138) and presence of PVD (OR 1.34; CI 0.823–2.197; P = 0.238) were included in the multivariate logistic regression, but neither were independently associated with failure.ConclusionDefinitive antibiotic therapy was not associated with a significant decrease in treatment failure.Disclosures All authors: No reported disclosures.

1521. Evaluation of the Microbiology of Intraabdominal Infections in Children and Implications for Treatment and Outcomes

BackgroundAcute appendicitis is the most common surgical emergency in pediatric medicine. Pseudomonas aeruginosa has been reported in up to 23% of intraoperative cultures though current recommendations do not specify the need for antipseudomonal coverage for preoperative treatment. Prior to transitioning the empiric antibiotic regimen used in the management of perforated appendicitis from an antipseudomonal agent to a simplified daily antibiotic regimen, we conducted a retrospective review of bacterial cultures obtained from intraabdominal fluid collections and antibiotic regimens in children that underwent surgical treatment of perforated appendicitis and/or intraabdominal abscesses.MethodsA retrospective chart review of electronic medical records was conducted for pediatric patients admitted with a diagnosis of perforated appendicitis and/or intraabdominal abscess between April 1, 2016 and April 30, 2018.ResultsSeventy-two patients met inclusion criteria for the study with abscess identified prior to surgery in 11 patients (42.3%). Intraabdominal cultures were obtained in 48 patients (66.7%). The predominant organisms isolated were Escherichia coli, Bacteroides fragilis, and alpha-hemolytic Streptococcus. P. aeruginosa was identified in 12 (24%) cultures and never as a single organism. The majority of patients received piperacillin/tazobactam empirically (91.7%) with a median duration of 5 days (IQR 2). Forty-four patients (61.1%) received oral antibiotics to continue therapy after discharge and 75% received amoxicillin/clavulanate. Of the 12 patients with P. aeruginosa isolated, all patients received piperacillin/tazobactam empirically and 8 (66.7%) were transitioned to oral antibiotics to complete therapy, of which only two regimens retained antipseudomonal coverage.ConclusionMajority of intraabdominal cultures were polymicrobial and the isolation of P. aeruginosa did not appear to impact the choice of definitive antimicrobial therapy. The predominant organisms identified suggest that a non-antipseudomonal regimen (i.e., cephalosporin with metronidazole) may be considered for empiric antibiotic therapy for cases of perforated appendicitis.Disclosures All authors: No reported disclosures.

Potential Clinical Effects of a Novel Rapid Diagnostic Panel for Pediatric Musculoskeletal Infections.

A direct-from-source rapid musculoskeletal diagnostic panel (MDP) was validated recently. We compared clinical measures to theoretical time points had MDP results been available. The MDP would have significantly decreased the time to pathogen identification (7 hours), time to definitive antimicrobial therapy (22 hours), and hospital length of stay (26.4 hours).

2061. Impact of a Penicillin-Binding Protein 2a Rapid Diagnostic Test on Patients Who Present with Staphylococcus aureus Orthopedic Hardware Infections

BackgroundWaiting for culture availability from orthopedic hardware (HW) infections delays patient discharge and time to definitive antimicrobial therapy. In February 2017, Vanderbilt University Hospital (VUH) implemented a penicillin-binding protein 2a-based rapid diagnostic, Alere®, to differentiate methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) from tissue sample growth. In other settings, use of Alere® demonstrated decreased time to definitive therapy with and without stewardship intervention. However, no studies to date have examined the impact of Alere® in the orthopedic HW infection population.MethodsWe performed a retrospective study of patients ≥18 years of age admitted to VUH with a culture-positive, monomicrobial, S. aureus orthopedic HW infection. Select ICD-10 codes related to orthopedic HW infections were used to identify potential patients. Exclusion criteria included concomitant bacteremia or polymicrobial infections. Patients with sterile site cultures obtained from August 2016 to January 2017 were included in the pre-Alere® group and February 2017 to September 2017 in the post-Alere® group. The primary outcome was time to appropriate antibiotic, defined as cefazolin or nafcillin for MSSA, and vancomycin for MRSA. Daptomycin and linezolid were acceptable alternatives in the case of prior vancomycin failure, or severe, documented reaction to vancomycin.ResultsICD-10 codes identified a total of 331 patients, with 29 (8.7%) demonstrating monomicrobial S. aureus HW infections (52% MSSA). There were 11 (38%) and 18 (62%) patients in pre- and post-Alere® groups, respectively. Alere® results provided definitive methicillin susceptibility 31.9 (range 19.5–46.1) hours before standard culture results. Time to appropriate antibiotic was 41.8 hours less in post-Alere® group (P = 0.009). Duration of empiric Gram-negative coverage was significantly reduced in the post-Alere® group (P = 0.029). Overall length of stay was unchanged between the groups (P = 0.873).ConclusionIntroduction of Alere® reduced time to appropriate therapy and reduced empiric Gram negative coverage in patients being treated for orthopedic hardware infections.Disclosures All authors: No reported disclosures.

Antimicrobial consumption, costs and resistance patterns: a two year prospective study in a Romanian intensive care unit

BackgroundDue to the vulnerable nature of its patients, the wide use of invasive devices and broad-spectrum antimicrobials used, the intensive care unit (ICU) is often called the epicentre of infections. In the present study, we quantified the burden of hospital acquired pathology in a Romanian university hospital ICU, represented by antimicrobial agents consumption, costs and local resistance patterns, in order to identify multimodal interventional strategies.MethodsBetween 1st January 2012 and 31st December 2013, a prospective study was conducted in the largest ICU of Western Romania. The study group was divided into four sub-samples: patients who only received prophylactic antibiotherapy, those with community-acquired infections, patients who developed hospital acquired infections and patients with community acquired infections complicated by hospital-acquired infections. The statistical analysis was performed using the EpiInfo version 3.5.4 and SPSS version 20.ResultsA total of 1596 subjects were enrolled in the study and the recorded consumption of antimicrobial agents was 1172.40 DDD/ 1000 patient-days.The presence of hospital acquired infections doubled the length of stay (6.70 days for patients with community-acquired infections versus 16.06/14.08 days for those with hospital-acquired infections), the number of antimicrobial treatment days (5.47 in sub-sample II versus 11.18/12.13 in sub-samples III/IV) and they increased by 4 times compared to uninfected patients. The perioperative prophylactic antibiotic treatment had an average length duration of 2.78 while the empirical antimicrobial therapy was 3.96 days in sample II and 4.75/4.85 days for the patients with hospital-acquired infections. The incidence density of resistant strains was 8.27/1000 patient-days for methicilin resistant Staphylococcus aureus, 7.88 for extended spectrum β-lactamase producing Klebsiella pneumoniae and 4.68/1000 patient-days for multidrug resistant Acinetobacter baumannii.ConclusionsSome of the most important circumstances collectively contributing to increasing the consumption of antimicrobials and high incidence densities of multidrug-resistant bacteria in the studied ICU, are represented by prolonged chemoprophylaxis and empirical treatment and also by not applying the definitive antimicrobial therapy, especially in patients with favourable evolution under empirical antibiotic treatment. The present data should represent convincing evidence for policy changes in the antibiotic therapy.

Optimal duration of antimicrobial therapy for uncomplicated Gram-negative bloodstream infections.

Optimal antimicrobial treatment duration for Gram-negative bloodstream infection (BSI) remains unclear. This retrospective cohort study examined effectiveness of short (7-10days) and long (>10days) courses of antimicrobial therapy for uncomplicated Gram-negative BSI. Hospitalized adults with uncomplicated Gram-negative BSI at Palmetto Health hospitals in Columbia SC, USA from January 1, 2010 to December 31, 2013 were identified. Multivariate Cox proportional hazards regression with propensity score adjustment was used to examine risk of treatment failure in the two groups. During the study period, 117 and 294 patients received short and long courses of antimicrobial therapy for uncomplicated Gram-negative BSI, respectively. Overall, the median age was 67years, 258 (63%) were women, 282 (69%) had urinary source of infection, and 271 (66%) had BSI due to Escherichia coli. The median duration of antimicrobial therapy was 8.5 and 13.3days in the short and long treatment groups, respectively. After adjustment for the propensity to use a short course of therapy, risk of treatment failure was higher in patients receiving short compared to long courses of antimicrobial agents (HR 2.60, 95% CI: 1.20-5.53, p=0.02). Other risk factors for treatment failure included liver cirrhosis (HR 5.83, 95% CI: 1.89-15.02, p=0.004) and immune compromised status (HR 4.30, 95% CI: 1.57-10.80, p=0.006). Definitive antimicrobial therapy with intravenous or highly bioavailable oral agents was associated with reduced risk of treatment failure (HR 0.33, 95% CI: 0.14-0.73, p=0.006). The current results support common clinical practice of 2weeks of antimicrobial therapy for uncomplicated Gram-negative BSI.

Characterisation of extended-spectrum β-lactamase and AmpC β-lactamase-producing Enterobacteriaceae isolated from companion animals in New Zealand

AIMS: To assess the occurrence of, and characterise, extended-spectrum β-lactamase (ESBL) and AmpC β-lactamase (AmpC)-producing Enterobacteriaceae isolated by veterinary diagnostic laboratories from infection sites in companion animals in New Zealand.METHODS: Selected Enterobacteriaceae isolates were submitted by seven New Zealand veterinary diagnostic laboratories. They were isolated from infection sites in companion animals between June 2012 and June 2013, and were resistant to amoxicillin-clavulanic acid, fluoroquinolones, or any combination of two or more antimicrobials. Based on disk diffusion test results, the isolates were phenotypically categorised according to production of ESBL and AmpC. Genes for ESBL and AmpC production were amplified by PCR and sequenced. Escherichia coli isolates were also typed by multilocus sequence typing.RESULTS: A total of 115 isolates matching the inclusion criteria were obtained from the participating laboratories, of which 74 (64%) originated from dogs and 29 (25%) from cats. Seven bacterial species were identified, of which E. coli was the most common (87/115, 76%). Of the 115 isolates, 10 (9%) expressed the ESBL phenotype, 43 (37%) the AmpC phenotype, and seven (6%) both ESBL and AmpC phenotypes. Of the 60 ESBL and AmpC-producing isolates, 36 (60%) were E. coli. Amongst these isolates, 27/60 (45%) were classified as multidrug resistant, compared with 15/55 (27%) non-ESBL or AmpC-producing isolates (p<0.01). Ninety five isolates were resistant to amoxicillin-clavulanic acid and 58 (61%) of these were ESBL or AmpC-producing. The predominant ESBL genes were blaCTX-M-14 and blaCTX-M-15, and the dominant plasmid-encoded AmpC gene was blaCMY-2. Thirty-eight E. coli multilocus sequence types (ST) were identified, and the most prevalent were ST12 (12/89, 13%), ST131 (6/89, 7%) and ST648 (6/89, 7%). ESBL and AmpC-producing isolates accounted for 35/1,082 (3.2%) of the Enterobacteriaceae isolated by one laboratory network over the study period.CONCLUSIONS AND CLINICAL RELEVANCE: ESBL and AmpC-producing Enterobacteriaceae were associated with clinical infections in companion animals in New Zealand, and were often multidrug resistant. In this study, these organisms accounted for <5% of all Enterobacteriaceae isolated from infection sites by one laboratory network, but their prevalence among isolates resistant to amoxicillin-clavulanic acid was 61%. Therefore routine secondary testing for ESBL and AmpC production by Enterobacteriaceae that are resistant to amoxicillin-clavulanic acid in primary testing could improve the accuracy of definitive antimicrobial therapy in companion animals in New Zealand.

Don’t Ask, Don’t Tell: Quality of β-Lactam Allergy Assessment in Patients with Methicillin-Susceptible Staphylococcus aureus (MSSA) Infections at a Tertiary-Care VA Medical Center

Backgroundβ-Lactams (BL) are optimal therapy for MSSA infections; however allergies to BL are reported frequently and may alter antibiotic selection for these infections. Limited data exist evaluating the frequency at which a new BL allergy history (AH) is taken when patients present with MSSA infections.MethodsWe conducted a 10-year retrospective review of patients treated for MSSA infections with report of BL allergy in the allergy section of the electronic medical record (EMR). Acquisition of new AH on initiation of empiric or definitive MSSA antimicrobial therapy was reviewed. Standard allergy characterization questions assess (1) age at BL reaction, (2) recollection of reaction, (3) timing from BL to reaction, (4) route of administration, (5) rationale for BL, (6) prior BL tolerance, (7) confounding medications, and (8) symptom resolution. A new AH was considered inappropriate if 0/8 items were addressed. Types of infection, types of allergic reaction, BL agents, adverse events and treatment failure rates were also analyzed.ResultsProviders seeing 142 MSSA-infected patients with EMR-based BL AH did not gather any new AH 59% of the time (83/142). Of those, 36% (30/83) of patients had an “unknown” AH in the EMR, yet no new AH was taken prior to MSSA therapy selection. When a new AH was taken, previous BL exposure (29%), recall of reaction (41%), and symptoms (83%) were the most asked questions The likelihood of exploring past BL exposure (predictor of ability to tolerate current BL) increased from 17 to 42% when 2 vs. 3 questions were assessed, respectively. Most interestingly, new provider-verified symptoms differed from prior documentation in the allergy section of the EMR 65% of the time. The most common MSSA infections treated were skin infections (34%) and bacteremia (32%). Overall, no significant differences in treatment failures and adverse events were found between patients treated with BL and non-BL therapy, perhaps due to heterogeneity of infection types.ConclusionIn ~40% of cases, new BL allergy histories were not obtained prior to initiating treatment of MSSA infections, despite our data suggesting AH reassessment uncovers new, clinically relevant information. Routine incorporation of better AH can enhance antimicrobial stewardship programs.Disclosures All authors: No reported disclosures.

IWGDF guidance on the diagnosis and management of foot infections in persons with diabetes.

RecommendationsClassification/diagnosis Diabetic foot infection must be diagnosed clinically, based on the presence of local or systemic signs or symptoms of inflammation (strong; low). Assess the severity of any diabetic foot infection using the Infectious Diseases Society of America/International Working Group on the Diabetic Foot classification scheme (strong; moderate). Osteomyelitis For an infected open wound, perform a probe‐to‐bone test; in a patient at low risk for osteomyelitis, a negative test largely rules out the diagnosis, while in a high‐risk patient, a positive test is largely diagnostic (strong; high). Markedly elevated serum inflammatory markers, especially erythrocyte sedimentation rate, are suggestive of osteomyelitis in suspected cases (weak; moderate). A definite diagnosis of bone infection usually requires positive results on microbiological (and, optimally, histological) examinations of an aseptically obtained bone sample, but this is usually required only when the diagnosis is in doubt or determining the causative pathogen's antibiotic susceptibility is crucial (strong; moderate). A probable diagnosis of bone infection is reasonable if there are positive results on a combination of diagnostic tests, such as probe‐to‐bone, serum inflammatory markers, plain X‐ray, magnetic resonance imaging (MRI) or radionuclide scanning (strong; weak). Avoid using results of soft tissue or sinus tract specimens for selecting antibiotic therapy for osteomyelitis as they do not accurately reflect bone culture results (strong; moderate). Obtain plain X‐rays of the foot in all cases of non‐superficial diabetic foot infection (strong; low). Use MRI when an advanced imaging test is needed for diagnosing diabetic foot osteomyelitis (strong; moderate). When MRI is not available or contraindicated, consider a white blood cell‐labelled radionuclide scan, or possibly single‐photon emission computed tomography (CT) and CT (SPECT/CT) or fluorine‐18‐fluorodeoxyglucose positron emission tomography/CT scans (weak; moderate). Assessing severity At initial evaluation of any infected foot, obtain vital signs and appropriate blood tests, debride the wound and probe and assess the depth and extent of the infection to establish its severity (strong; moderate). At initial evaluation, assess arterial perfusion and decide whether and when further vascular assessment or revascularization is needed (strong; low). Microbiological considerations Obtain cultures, preferably of a tissue specimen rather than a swab, of infected wounds to determine the causative microorganisms and their antibiotic sensitivity (strong; high). Do not obtain repeat cultures unless the patient is not clinically responding to treatment, or occasionally for infection control surveillance of resistant pathogens (strong; low). Send collected specimens to the microbiology laboratory promptly, in sterile transport containers, accompanied by clinical information on the type of specimen and location of the wound (strong; low). Surgical treatment Consult a surgical specialist in selected cases of moderate, and all cases of severe, diabetic foot infection (weak; low). Perform urgent surgical interventions in cases of deep abscesses, compartment syndrome and virtually all necrotizing soft tissue infections (strong; low). Consider surgical intervention in cases of osteomyelitis accompanied by spreading soft tissue infection, destroyed soft tissue envelope, progressive bone destruction on X‐ray or bone protruding through the ulcer (strong; low). Antimicrobial therapy While virtually all clinically infected diabetic foot wounds require antimicrobial therapy, do not treat clinically uninfected wounds with antimicrobial therapy (Strong; Low) Select specific antibiotic agents for treatment based on the likely or proven causative pathogens, their antibiotic susceptibilities, the clinical severity of the infection, evidence of efficacy of the agent for diabetic foot infection and costs (strong; moderate). A course of antibiotic therapy of 1–2 weeks is usually adequate for most mild and moderate infections (strong; high). Administer parenteral therapy initially for most severe infections and some moderate infections, with a switch to oral therapy when the infection is responding (strong; low). Do not select a specific type of dressing for a diabetic foot infection with the aim of preventing an infection or improving its outcome (strong; high). For diabetic foot osteomyelitis, we recommend 6 weeks of antibiotic therapy for patients who do not undergo resection of infected bone and no more than a week of antibiotic treatment if all infected bone is resected (strong; moderate). We suggest not using any adjunctive treatments for diabetic foot infection (weak; low). When treating a diabetic foot infection, assess for use of traditional remedies and previous antibiotic use and consider local bacterial pathogens and their susceptibility profile (strong; low).

The impact of previous hospitalization in the preceding 90 days on the outcome in critically ill patients with gram-negative bloodstream infection

We conducted a retrospective cohort study to evaluate the impact of previous hospitalization in the preceding 90 days on mortality in critically ill patients with gram-negative bloodstream infection (BSI) and to identify the risk factors for 30-day mortality in these patients. Of 89 critically ill patients with gram-negative BSI, 42 patients had previous hospitalization in the preceding 90 days. Multivariate Cox regression analysis revealed previous hospitalization in the preceding 90 days as a significant predictor for 30-day mortality (hazard ratio [HR], 2.10; 95% confidence interval [CI], 1.11–3.94; P = 0.022), along with Acute Physiology and Chronic Health Evaluation II score at BSI onset (HR, 1.08; 95% CI, 1.04–1.12; P < 0.001), liver cirrhosis (HR, 3.61; 95% CI, 1.46–8.94; P = 0.006), and inappropriate definitive antimicrobial therapy (HR, 4.28; 95% CI, 2.17–8.45; P < 0.001). The effect of previous hospitalization in the preceding 90 days should be considered in evaluating the risk for 30-day mortality when treating such patients, and further study is required.

Comparison of Commercial Antimicrobial Susceptibility Test Methods for Testing of Staphylococcus aureus and Enterococci against Vancomycin, Daptomycin, and Linezolid

Three commercial antimicrobial susceptibility testing (AST) methods were compared to broth microdilution for testing of Staphylococcus aureus and enterococci against vancomycin, daptomycin, and linezolid. Despite high levels of categorical agreement and essential agreement, vancomycin MICs determined by MicroScan were often 1 log2 concentration higher and MICs determined by Phoenix 1 log2 concentration lower. Daptomycin MICs were 1 to 2 log2 concentrations higher by all AST methods, except Etest, potentially impacting definitive antimicrobial therapy for bloodstream infections due to these organisms.

Relative efficacy of cefuroxime versus dicloxacillin as definitive antimicrobial therapy in methicillin-susceptible Staphylococcus aureus bacteraemia: a propensity-score adjusted retrospective cohort study

The objective of the present study was to compare the efficacy of cefuroxime with that of dicloxacillin as definitive antimicrobial therapy in methicillin-susceptible Staphylococcus aureus bacteraemia (MS-SAB) using a Danish bacteraemia database, information on the indication for antimicrobial therapy, multivariate adjustment and propensity score (PS) matching. This was a retrospective cohort study. MS-SAB cases from 1 January 2006 to 31 December 2008 were included from a total of seven hospitals in the greater Copenhagen area and seven hospitals in the North Denmark Region. Information including demographics, antimicrobial therapy and clinical condition was obtained. The physician's note detailing the indication for starting empirical antimicrobial therapy was given special attention. Hazard ratios (HRs) and 95% CIs for 30 day and 90 day mortality were calculated using PS-adjusted Cox proportional hazards regression analyses. In addition, PS matching was performed. A total of 691 patients with MS-SAB received either dicloxacillin (n = 368) or cefuroxime (n = 323) as definitive antimicrobial therapy. Twenty-eight different indications for empirical antimicrobial therapy were identified and grouped into eight categories. There was no statistically significant difference in 30 day mortality between the two groups (HR 1.02, 95% CI 0.68-1.52). Definitive antimicrobial therapy with cefuroxime was associated with increased 90 day mortality in a PS-adjusted multivariate analysis (HR 1.43, 95% CI 1.03-1.98) and in the PS matching (OR 1.65, 95% CI 1.06-2.56). Antimicrobial therapy for an indication of 'severe infection' was independently associated with 90 day mortality (HR 1.97, 95% CI 1.19-3.28). Definitive antimicrobial therapy with cefuroxime was associated with significantly higher 90 day mortality than was dicloxacillin therapy in patients with MS-SAB.