Optimal Antimicrobial Therapy Research Articles

Survival of a case of Bacillus cereus meningitis with brain abscess presenting as immune reconstitution syndrome after febrile neutropenia \u2013 a case report and literature review-

BackgroundBacillus cereus sometimes causes central nervous system infection, especially in compromised hosts. In cases of meningitis arising during neutropenia, CSF abnormalities tend to be subtle and can be easily overlooked, and mortality rate is high. We report a survived case of B. cereus meningitis/brain abscess in severe neutropenia, presenting as immune reconstitution syndrome.Case presentationA 54-year-old Japanese female with acute myelogenous leukemia developed B. cereus bacteremia and meningitis during consolidation chemotherapy. At the onset, she presented with mild meningism. She had marked leukocytopenia (WBC <100/μL, neutrophils 0/μL) and lumbar puncture yielded only mild pleocytosis. She was transferred to intensive care unit, and meropenem, linezolid and vancomycin was started. With intensive therapy, she recovered and once became afebrile. On day 19, however, her fever, meningism and consciousness level dramatically worsened despite recovery of bone marrow function. The antimicrobial chemotherapy was continued and finally she was cured with no complications.ConclusionsWith early diagnosis and prompt initiation and of antibiotics, the case was successfully treated without any sequelae. It is important to remember that, even under optimal antimicrobial therapy, bone marrow recovery can cause transient reaggravation of the disease. In such cases, timely and appropriate evaluation should be done to make the clinical decision to change, continue, or intensify treatment.

In Vitro Pharmacodynamic Analyses Help Guide the Treatment of Multidrug-Resistant Enterococcus faecium and Carbapenem-Resistant Enterobacter cloacae Bacteremia in a Liver Transplant Patient.

BackgroundInfections due to multidrug-resistant pathogens are particularly deadly and difficult to treat in immunocompromised patients, where few data exist to guide optimal antimicrobial therapy. In the absence of adequate clinical data, in vitro pharmacokinetic (PK)/pharmacodynamic (PD) analyses can help to design treatment regimens that are bactericidal and may be clinically effective. MethodsWe report a case in which in vitro pharmacodynamic analyses were utilized to guide the treatment of complex, recurrent bacteremias due to vancomycin-, daptomycin-, and linezolid-resistant Enterococcus faecium and carbapenem-resistant Enterobacter cloacae complex in a liver transplant patient. ResultsWhole-genome sequencing revealed unique underlying resistance mechanisms and explained the rapid evolution of phenotypic resistance and complicated intrahost genomic dynamics observed in vivo. Performing this comprehensive genotypic and phenotypic testing and time-kill analyses, along with knowledge of institution and patient-specific factors, allowed us to use precision medicine to design a treatment regimen that maximized PK/PD. ConclusionsThis work provides a motivating example of clinicians and scientists uniting to optimize care in the era of escalating antimicrobial resistance.

Enterococcal periprosthetic joint infection: clinical and microbiological findings from an 8-year retrospective cohort study

BackgroundTreatment of enterococcal periprosthetic joint infections (PJI) is challenging due to non-standardized management strategies and lack of biofilm-active antibiotics. The optimal surgical and antimicrobial therapy are unknown. Therefore, we evaluated characteristics and outcome of enterococcal PJI.MethodsConsecutive patients with enterococcal PJI from two specialized orthopedic institutions were retrospectively analyzed. Both institutions are following the same diagnostic and treatment concepts. The probability of relapse-free survival was estimated using Kaplan-Meier survival curves and compared by log-rank test. Treatment success was defined by absence of relapse or persistence of PJI due to enterococci or death related to enterococcal PJI. Clinical success was defined by the infection-free status, no subsequent surgical intervention for persistent or perioperative infection after re-implantation and no PJI-related death within 3 months.ResultsIncluded were 75 enterococcal PJI episodes, involving 41 hip, 30 knee, 2 elbow and 2 shoulder prostheses. PJI occurred postoperatively in 61 episodes (81%), hematogenously in 13 (17%) and by contiguous spread in one. E. faecalis grew in 64 episodes, E. faecium in 10 and E. casseliflavus in one episode(s). Additional microorganism(s) were isolated in 38 patients (51%). Enterococci were susceptible to vancomycin in 73 of 75 isolates (97%), to daptomycin in all 75 isolates, and to fosfomycin in 21 of 22 isolates (96%). The outcome data was available for 66 patients (88%). The treatment success after 3 years was 83.7% (95% confidence interval [CI]; 76.1–96.7%) and the clinical success was 67.5% (95% CI; 57.3–80.8%). In 11 patients (17%), a new PJI episode caused by a different pathogen occurred. All failures occurred within 3 years after surgery.ConclusionAbout half of enterococcal PJI were polymicrobial infections. The treatment success was high (84%). All treatment failures occurred within the first 3 years after revision surgery. Interestingly, 17% of patients experienced a new PJI caused by another pathogen at a later stage.Trial registrationThe study was retrospectively registered with the public clinical trial identification NCT0253022 at https://www.clinicaltrials.gov on 15 July 2015.

1512. Treatment of Staphylococcus aureus Bacteremia in a Pediatric Population: A Retrospective Cohort Analysis

Background Staphylococcus aureus bacteremia (SAB) is a well-known cause of morbidity in pediatric patients; however, limited data are available regarding optimal antimicrobial therapy. The purpose of this study was to assess treatment outcomes associated with intravenous (IV) vs. oral (PO) stepdown treatment of SAB in a pediatric population.MethodsThis study evaluated patients who were admitted between July 2012 and August 2018, between the ages of 3 months and 18 years, had a blood culture positive for S. aureus, and received at least 72 hours of inpatient treatment. Exclusion criteria were as follows: pregnancy, death within 72 hours of initial culture, hospice/palliative care, polymicrobial bacteremia, and previous SAB within the study period. The primary endpoint was 30-day readmission rates. Secondary endpoints included hospital length of stay and all-cause inpatient mortality.ResultsIn total, 101 patients were included (43 IV therapy alone; 58 PO stepdown). The median age was 7.9 years (IQR, 3.0, 12.2; range 4 months to 16.7 years), and 52.5% were male. The most common primary foci of infection were osteomyelitis (n = 32), device-associated infections (n = 23), and skin/soft-tissue infections (n = 8). Most patients (56.4%) had no comorbidities. There were no significant differences in comorbidities between groups except the IV group had significantly more immunosuppressed patients (30.2% vs. 1.7%; P < 0.001). Methicillin resistance was noted in 56.4% of patients (62.8% IV group vs. 51.7% PO stepdown; P = 0.313). The most common IV agents were vancomycin (n = 51) and anti-Staphylococcal penicillins (n = 21), while the most common PO agents were clindamycin (n = 29) and cephalexin (n = 20). Thirty-day readmission occurred in 25.6% (n = 10) of patients receiving full-course IV therapy and 5.3% (n = 3) in the PO stepdown group among survivors (P = 0.006; n = 96). Median length of stay was 11.0 days (IQR, 8.0, 21.0) in the IV group and 7.0 days (IQR, 5.0, 11.0) in the PO stepdown group (P = 0.001). All-cause inpatient mortality occurred in four patients (9.3%) in the IV group compared with one (1.7%) in the PO stepdown group (P = 0.160).ConclusionPatients in the PO stepdown group had a low rate of 30-day readmissions and had a significantly shorter hospital length of stay than patients who received a full IV course.Disclosures All authors: No reported disclosures.

395. Safety and Tolerability of Rifampin in Staphylococcal Orthopedic Infections

BackgroundRifampin is part of optimal combination antimicrobial therapy for staphylococcal foreign-body infections, including periprosthetic joint infections (PJI) in cases of retained prostheses. However, rifampin can have important drug interactions, can cause hepatotoxicity and other organ toxicity, and can induce treatment-limiting side effects. Although rifampin safety and tolerability is well-described in tuberculosis patients, its use in orthopedic infections is poorly described. We therefore analyzed the safety and tolerability of rifampin in patients with staphylococcal hip and knee PJIs treated with implant retention.MethodsA retrospective institutional PJI database was queried to identify all staphylococcal PJI cases treated with implant retention, from 2008 to 2016. Patient demographics, comorbidities, and antibiotic treatment course were collected. The Chi-square or Fisher’s exact test was used for comparisons between rifampin-tolerant (RT) and -intolerant (RI) subgroups.Results80 patients were included, of which 75 (94%) began rifampin. Of the 75 who received rifampin, 23% (17/75) were RI. The median duration of rifampin for RT was 3.0 months (range 1–60) and 0.75 months for RI (range 0.1–3). Reasons for RI included allergies (N = 6), GI toxicity (N = 5), increased liver function tests (N = 2), leukopenia (N = 2), acute kidney injury (N = 1), exacerbated epilepsy (possibly due to low phenytoin; N = 1), and vasculitis (N = 1). Patient age, sex, and Charlson comorbidity index did not predict rifampin intolerance. In 5/80 (6%) patients who never received rifampin, reasons included liver disease, drug interactions, and rifampin resistance. Overall, 27% (22/80) could not be adequately treated with rifampin.ConclusionIn this study cohort of PJI patients, contraindications to rifampin initiation were infrequent, but discontinuation due to intolerance, allergy, or toxicity occurred in nearly a quarter of patients. Drug-drug interactions can preclude its use, or may cause important medication switches in critical areas such as anticoagulation, epilepsy treatment, and HIV care. Research into the anti-staphylococcal efficacy and safety of alternative rifamycins (such as rifabutin and rifapentine) in patients with staphylococcal hardware infections is warranted.Disclosures All authors: No reported disclosures.

854. Impact of Antimicrobial Stewardship and Rapid Diagnostics in Children with Staphylococcus aureus Bacteremia

BackgroundRapid diagnostic testing (RDT) in combination with antimicrobial stewardship programs (ASPs) has been associated with improved outcomes in adults with Staphylococcus aureus bacteremia (SAB). Data in children are lacking. In January 2017, Atrium Health implemented a pediatric ASP with blood culture RDT. The objective of this study was to determine the impact of those interventions.MethodsThis was a retrospective, multicenter, quasi-experimental study of children ≤18 years with monomicrobial SAB from March 2015 to August 2016 (pre-intervention; PRE) and March 2017 to August 2018 (post-intervention; POST). The primary outcome was time to an optimal antibiotic. Secondary outcomes included time to effective antibiotic, total antibiotic exposure in the first 5 days, duration of bacteremia, infectious diseases (ID) consultation, time to central line removal, hospital and pediatric ICU length of stay (LOS), need for vasopressors or intubation, recurrence of SAB within 90 days, and inpatient mortality.ResultsOf 101 patients with SAB, 32 and 36 met inclusion criteria for the PRE and POST groups, respectively. The median time to optimal antimicrobial therapy decreased by 23 hours (PRE 44.3 hours vs. POST 21.3 hours; P = 0.008). Duration of bacteremia (65h vs. 40.9 hours; P = 0.028) and mortality (12.5% vs. 0%; P = 0.044) was also significantly reduced. Differences in median time to effective therapy (7 hours vs. 5.1 hours; P = 0.74), total antibiotic exposure in the first 5 days (160.4 hours vs. 152 hours; P = 0.4), hospital LOS (9.9 vs. 8.5 days; P = 0.25), and pediatric ICU LOS (7 vs. 4 days; P = 0.11) did not meet statistical significance, but trended downward. The POST group had more patients with ID consultation (78% vs. 89%, P = 0.23) and shorter time to central line removal (68 hours vs. 20 hours; P = 0.037). There was no difference in the need for vasopressors (3 vs. 3 patients; P = 0.99) or intubation (2 vs. 4 patients; P = 0.68). Throughout the study period, recurrence of SAB only occurred in one patient (PRE).ConclusionConcurrent implementation of RDT and an ASP in pediatric patients with SAB decreased time to optimal antimicrobial therapy, duration of bacteremia, and mortality. RDT coupled with timely feedback from an ASP contributed to improved SAB management and clinical outcomes in children.Disclosures All Authors: No reported Disclosures.

1998. Impact of Rapid Blood Culture Identification with Real-Time Antimicrobial Stewardship (ASP) in Patients with Staphylococcus aureus (S. aureus) and Enterococcus spp. Bacteremia at a Large Academic Medical Center

BackgroundThe initiation of appropriate antimicrobial therapy is dependent on timely identification of the pathogen. FilmArray Blood Culture Identification Panel (BCID) is a rapid, multiplex polymerase chain reaction (PCR) panel that identifies 24 pathogens and 3 antibiotic resistance genes associated with bloodstream infections within 1 hour of growth. The purpose of this study was to compare the clinical impact of rapid BCID testing vs. standard blood culture processing, both coupled with real-time ASP, in patients with S. aureus and Enterococcus spp. bacteremia.MethodsThis was a single-center, retrospective chart review conducted as a pre-post intervention quasi-experimental study. The pre-intervention group included adult patients with S.aureus and Enterococcus spp. bacteremia identified by standard blood culture processing (PRE) and the post-intervention group included those identified by rapid BCID testing (POST). The primary endpoint was time in hours from positive Gram stain to initiation of optimal antimicrobial therapy [defined as vancomycin (VAN), linezolid (LZD), daptomycin (DAP), or ceftaroline for methicillin-resistant S. aureus (MRSA); nafcillin or cefazolin for methicillin-susceptible S. aureus (MSSA); DAP or LZD for VAN-resistant Enterococcus (VRE); VAN or ampicillin (if susceptible) for VAN-susceptible Enterococcus (VSE)]. Secondary endpoints included time to active therapy (defined as an antimicrobial to which the organism was susceptible), time to identification of pathogen, length of hospital stay (LOS) after positive culture, and 30-day mortality.Results132 patients were included. Mean time to optimal therapy decreased from 21.4 hours PRE to 10.7 hours POST (P = 0.048). Time to optimal therapy was shorter POST for MSSA [59.2 hours PRE vs. 25.8 hours POST (P < 0.001)] and VRE bacteremia [24.6 hours PRE vs. 5.6 hours POST (P = 0.005)]. Time to identification of pathogen decreased from 75.6 hours PRE to 2.7 hours POST (P < 0.001). Groups did not differ in time to active therapy, LOS, nor 30-day mortality.ConclusionAntimicrobial Stewardship coupled with rapid BCID testing significantly decreased time to pathogen identification as well as time to optimal therapy in patients with S. aureus and Enterococcus spp. bacteremia, most notably for MSSA and VRE.Disclosures All authors: No reported disclosures.

Perioperative prophylaxis with single-dose cefazolin for liver transplantation: a retrospective study.

Early infections are common during the first month after liver transplantation (LT), whereas no consensus exists on the optimal prophylactic antimicrobial therapy. We aimed to evaluate the effectiveness of cefazolin perioperative prophylaxis in LT. We documented our experience with single-dose cefazolin as prophylaxis for LT. Infections occurring within 30 days following LT during 2006-2015 were documented retrospectively. Univariate and multivariate analyses of risk factors for infection were carried out. Among 113 LT recipients receiving cefazolin as prophylaxis, infections occurred in 50 (44%) patients, including surgical site infections (n=24, 21%) and bacteremia (n=14, 12%). Bacteria resistant to cefazolin were documented in 59/72 (82%) isolates. Enterococcal infections were documented in 6% (7/113). Almost half of the infections (44%) occurred in the first week following LT and the vast majority within 2 weeks. The 30-day mortality rate (7%, 8/113) was significantly higher among infected patients (7/50, 14% vs. 1/63, 1.6%, P=0.011). Model for End-stage Liver Disease score, age, and requirement for at least 5 U of packed red cells during transplantation were predictive for postoperative infections. In our center, cefazolin was insufficient as perioperative prophylaxis in LT. We suggest that all LT recipients should receive antibiotic prophylaxis targeting microorganisms on the basis of local bacterial ecology and patterns of resistance irrespective of preoperative or intraoperative risk assessment.

PSI-25 development of local Kansas E. coli UTI antibiograms to improve antimicrobial stewardship in companion animal medicine

Abstract Urinary tract infections are common in dogs, but rare in cats. Antimicrobial susceptibility testing of urine isolates is required to determine optimal antimicrobial therapy, but empirical antimicrobial guidelines are needed while culture is pending or if testing is declined. Antibiograms are summaries of local susceptibility trends that assist clinicians in selecting empirical antimicrobial therapy. Antibiograms were developed from E. coli feline (N = 138) and canine (N = 640) urinary isolates submitted by the KSU Veterinary Health Center and private veterinary practices from 2013–2017. Results showed a high prevalence of resistance among feline isolates to amoxicillin-clavulanate (99.3%, S ≤ 0.25) and ampicillin (99.3%, S ≤ 0.25), but lower prevalence among canine isolates (amoxicillin/clavulanate 7.7% S ≤ 8), ampicillin 46.7%, S ≤ 8). Resistance to other antimicrobials was uncommon, with no antimicrobial agents demonstrating resistance above 6% in feline isolates, or above 14% in canine isolates. Canine isolates from private veterinary practices had increased resistance as compared with KSU isolates to orbifloxacin (9.5% vs 0.1%) and pradofloxaxin (9.4% vs 0.1%). Application of different breakpoints and differences in antibiotic exposures may explain the disparity of Beta-Lactam resistance between cats and dogs. Different use patterns between hospitals may explain the disparity between fluoroquinolone resistance. These findings emphasize the need for definitive urine culture and susceptibility testing in pets with UTIs, so that appropriate and effective antimicrobial therapy can be prescribed. Veterinary clinicians in Kansas can use these antibiogram results in addition to following stewardship guidelines to maximize successful UTI therapy for veterinary patients and minimize development of antimicrobial resistance for the One Health community.

Clinical Impact of Rapid Species Identification From Positive Blood Cultures With Same-day Phenotypic Antimicrobial Susceptibility Testing on the Management and Outcome of Bloodstream Infections.

Timely availability of microbiological results from positive blood cultures is essential to enable early pathogen-directed therapy. The Accelerate Pheno system (ADX) is a novel technology using fluorescence in situ hybridization for rapid species identification (ID) and morphokinetic bacterial analysis for phenotypic antimicrobial susceptibility testing (AST), with promising results. Yet the impact of this technology on clinical management and patient outcome remains unclear. We conducted a quasiexperimental before-and-after observational study and analyzed 3 groups with different diagnostic and therapeutic pathways following recent integration of ADX: conventional microbiological diagnostics with and without antimicrobial stewardship program (ASP) intervention, and rapid diagnostics (ADX in addition to conventional standard) with ASP intervention. Primary endpoints were time to adequate, to optimal and to step-down antimicrobial therapy. Secondary endpoints were antimicrobial consumption, in-hospital mortality, length of stay (LOS), and the incidence of Clostridioidesdifficile infection (CDI). Two hundred four patients (conventional diagnostics, n = 64; conventional diagnostics + ASP, n = 68; rapid diagnostics + ASP; n = 72) were evaluated. The use of ADX significantly decreased time from Gram stain to ID (median, 23 vs 2.2 hours, P < .001) and AST (median, 23 vs 7.4 hours, P < .001), from Gram stain to optimal therapy (median, 11 vs 7 hours, P = .024) and to step-down antimicrobial therapy (median, 27.8 vs 12 hours, P = .019). However, groups did not differ in antimicrobial consumption, duration of antimicrobial therapy, mortality, LOS, or incidence of CDI. Use of ADX significantly reduced time to ID and AST as well as time to optimal antimicrobial therapy but did not affect antimicrobial consumption and clinical outcome.

Fast and reliable determination of Escherichia coli susceptibility to antibiotics: Infrared microscopy in tandem with machine learning algorithms.

Antimicrobial drugs have an important role in controlling bacterial infectious diseases. However, the increasing resistance of bacteria to antibiotics has become a global health care problem. Rapid determination of antimicrobial susceptibility of clinical isolates is often crucial for the optimal antimicrobial therapy. The conventional methods used in medical centers for susceptibility testing are time-consuming (>2 days). Two bacterial culture steps are needed, the first is used to grow the bacteria from urine on agar plates to determine the species of the bacteria (~24 hours). The second culture is used to determine the susceptibility by growing colonies from the first culture for another 24 hours. Here, the main goal is to examine the potential of infrared microscopy combined with multivariate analysis, to reduce the time it takes to identify Escherichia coli susceptibility to antibiotics and to determine the optimum choice of antibiotic to which the bacteria will respond. E coli colonies of the first culture from patients with urinary tract infections (UTI) were examined for the bacterial susceptibility using Fourier-transform infrared (FTIR). Our results show that it is possible to determine the optimum choice of antibiotic with better than 89% sensitivity, in the time span of few minutes, following the first culture.

A randomised controlled trial of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDITOF-MS) versus conventional microbiological methods for identifying pathogens: Impact on optimal antimicrobial therapy of invasive bacterial and fungal infections in Vietnam

We assessed the impact of MALDITOF-MS on the timeliness of optimal antimicrobial therapy through a parallel-arm randomised controlled trial in two hospitals in Vietnam. We recruited patients with a pathogen (bacterial or fungal) cultured from a normally sterile sample. Samples were randomly assigned (1:1) to identification by MALDITOF-MS or conventional diagnostics. The primary outcome was the proportion on optimal antimicrobial therapy within 24 h of positive culture, determined by a blinded independent review committee. Trial registered at ClinicalTrials.gov (NCT02306330). Among 1005 randomised patients, pathogens were isolated from 628 (326 intervention, 302 control), with 377 excluded as likely contaminants or discharged/died before positive culture. Most isolates were cultured from blood (421/628, 67.0%). The proportion receiving optimal antimicrobial therapy within 24 h (the primary outcome) or 48 h of growth was not significantly different between MALDITOF-MS and control arms (135/326, 41.4% vs 120/302, 39.7%; Adjusted Odds ration (AOR) 1.17, p = 0.40 and 151/326, 46.3% vs 141/302, 46.7%; AOR 1.05 p = 0.79, respectively). MALDITOF-MS, in the absence of an antimicrobial stewardship programme, did not improve the proportion on optimal antimicrobial therapy at 24 or 48 h after first growth in a lower-middle income setting with high rates of antibiotic resistance.

Ideal and Actual Impact of Rapid Diagnostic Testing and Antibiotic Stewardship on Antibiotic Prescribing and Clinical Outcomes in Children With Positive Blood Cultures.

Implementing matrix-assisted laser desorption ionization-time of flight and multiplex polymerase chain reaction has been associated with decreased mortality and hospital length of stay in adults, but the impact in pediatrics is less understood. This pre-post quasi-experimental study compared antibiotic prescribing for positive blood cultures in patients ≤21 years of age collected in 2012 (preintervention) and in 2015 (after matrix-assisted laser desorption ionization-time of flight/multiplex polymerase chain reaction). Time to effective and optimal antimicrobial therapy was evaluated using Cox proportional hazards regression. Time to ideal optimal therapy was estimated as the earliest potential initiation of optimal therapy. Antibiotic use and clinical outcomes were measured. There were 242 and 192 positive monomicrobial blood cultures in 2012 and 2015, respectively. Postintervention, time to optimal therapy (73.8 vs. 48.8 hours; P < 0.001) and organism identification (55.6 vs. 29.5 hours; P < 0.001) were reduced, and patients were more likely to receive optimal therapy by 7 days (hazard ratio, 1.85; P < 0.001). In the ideal scenario in 2015, there was an 8.8-hour delay in initiating optimal therapy based on the time that sufficient microbiologic data were available. Postintervention, time to effective therapy (2.8 vs. 2.7 hours; P = 0.782) and clinical outcomes did not differ. Unnecessary antibiotic duration for probable contaminants (skin flora) (43.1 vs. 29.7 hours; P = 0.027), vancomycin for methicillin-sensitive Staphylococcus aureus (54.0 vs. 41.3 hours; P = 0.008) and nonpenicillin/ampicillin antibiotics for group A Streptococcus, group B Streptococcus and Enterococcus faecalis (87.2 vs. 33.4 hours; P < 0.001) were reduced postintervention. Rapid diagnostics reduced time to optimal antimicrobial therapy and unnecessary antibiotic use without worse clinical outcomes.

Optimal antimicrobial therapy and antimicrobial stewardship in sepsis and septic shock

The management of sepsis and septic shock remains challenging. The aim is to apply the optimal antimicrobial therapy and antimicrobial stewardship to patients in state of sepsis or septic shock. To reduce the mortality of sepsis and septic shock, it is critical to promptly administer the appropriate antibiotics with an accurate diagnosis. De-escalation is needed 48 to 72 hours after the first administration of antibiotics depending on the findings of causative pathogens. In the case of antibiotic resistance, the importance of an antibiotic stewardship program is increasingly being emphasized. Antimicrobial stewardship implies coordinated interventions designed to improve the appropriate use of antibiotics by promoting the selection of an optimal drug regimen such as dosing, duration of therapy, and route of administration. An antibiotic stewardship program may also be applied to patients of both sepsis and septic shock. Efforts such as the selection of appropriate empirical antibiotics, de-escalation, and determination of whether to stop antibiotics with procalcitonin may improve the clinical prognosis of patients with sepsis as well as the successful implementation of an antibiotic stewardship program.

Interplay between Rapid Diagnostic Tests and Antimicrobial Stewardship Programs among Patients with Bloodstream and Other Severe Infections.

Antimicrobial stewardship programs (ASPs) aim to provide optimal antimicrobial therapy to patients quickly to improve the likelihood of overcoming infection while reducing the risk of adverse effects. Rapid diagnostic tests (RDTs) for infectious diseases have become an integral tool for ASPs to achieve these aims. This review explored the demonstrated clinical value of longer-standing technologies and implications of newer RDTs from an antimicrobial stewardship perspective. Based on available literature, the focus was on the use of RDTs in bloodstream infections (BSIs), particularly those that perform organism identification and genotypic resistance detection, phenotypic susceptibility testing, and direct specimen testing. Clinical implications of rapid testing among respiratory, central nervous system, and gastrointestinal infections are also reviewed. Coupling RDTs with ASPs facilitates the appropriate and timely use of test results, translating into improved patient outcomes through optimization of antimicrobial use. These benefits are best demonstrated in the use of RDT in BSIs. Rapid phenotypic susceptibility testing offers the potential for early pharmacokinetic/pharmacodynamic optimization, and direct specimen testing on blood may allow ASPs to initiate appropriate therapy and/or tailor empiric therapy even sooner than other RDTs. RDTs for respiratory, central nervous system, and gastrointestinal illnesses have also shown significant promise, although more outcome studies are needed to evaluate their full impact.

Predictors of Time to Effective and Optimal Antimicrobial Therapy in Patients With Positive Blood Cultures Identified via Molecular Rapid Diagnostic Testing.

Antimicrobial stewardship (AMS) programs integrated with rapid diagnostic tests optimize patient outcomes and reduce time to effective therapy (TTET) and time to optimal therapy (TTOT). This study identifies predictors of TTET and TTOT among patients with positive blood cultures and identifies limitations to current TTOT definitions and outcomes.

Comparison of Pharmacist-Directed Management of Multiplex PCR Blood Culture Results with Conventional Microbiology Methods on Effective and Optimal Therapy within a Community Hospital.

Multiplex PCR combined with a pharmacist-driven reporting protocol was compared to the standard of care within a community hospital to evaluate initial changes after notification of a positive blood culture. The intervention group demonstrated decreased times to changes in antimicrobial therapy (P = 0.0081), increased changes to optimal antimicrobial therapy (P = 0.013), and decreased vancomycin use for coagulase-negative staphylococcus contaminants (P < 0.01) with multiplex PCR implementation and pharmacist intervention.

Applying Rapid Whole-Genome Sequencing To Predict Phenotypic Antimicrobial Susceptibility Testing Results among Carbapenem-Resistant Klebsiella pneumoniae Clinical Isolates.

Standard antimicrobial susceptibility testing (AST) approaches lead to delays in the selection of optimal antimicrobial therapy. Here, we sought to determine the accuracy of antimicrobial resistance (AMR) determinants identified by Nanopore whole-genome sequencing in predicting AST results. Using a cohort of 40 clinical isolates (21 carbapenemase-producing carbapenem-resistant Klebsiella pneumoniae, 10 non-carbapenemase-producing carbapenem-resistant K. pneumoniae, and 9 carbapenem-susceptible K. pneumoniae isolates), three separate sequencing and analysis pipelines were performed, as follows: (i) a real-time Nanopore analysis approach identifying acquired AMR genes, (ii) an assembly-based Nanopore approach identifying acquired AMR genes and chromosomal mutations, and (iii) an approach using short-read correction of Nanopore assemblies. The short-read correction of Nanopore assemblies served as the reference standard to determine the accuracy of Nanopore sequencing results. With the real-time analysis approach, full annotation of acquired AMR genes occurred within 8 h from subcultured isolates. Assemblies sufficient for full resistance gene and single-nucleotide polymorphism annotation were available within 14 h from subcultured isolates. The overall agreement of genotypic results and anticipated AST results for the 40 K. pneumoniae isolates was 77% (range, 30% to 100%) and 92% (range, 80% to 100%) for the real-time approach and the assembly approach, respectively. Evaluating the patients contributing the 40 isolates, the real-time approach and assembly approach could shorten the median time to effective antibiotic therapy by 20 h and 26 h, respectively, compared to standard AST. Nanopore sequencing offers a rapid approach to both accurately identify resistance mechanisms and to predict AST results for K. pneumoniae isolates. Bioinformatics improvements enabling real-time alignment, coupled with rapid extraction and library preparation, will further enhance the accuracy and workflow of the Nanopore real-time approach.

The Clinical and Financial Impact of a Pharmacist-Driven Penicillin Skin Testing Program on Antimicrobial Stewardship Practices.

Purpose: Pharmacist-led penicillin skin testing (PST) was incorporated into antimicrobial stewardship at a community hospital to increase use of optimal antimicrobial therapy, reduce use of broad-spectrum agents, and reduce antimicrobial therapy-related costs. Methods: A clinical decision support software alert identified qualifying patients with penicillin allergies. Patients receiving a nonoptimal antimicrobial agent were prioritized for PST. Patients were excluded if they reported a history of extreme hypersensitivity to a penicillin agent, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, or mucocutaneous eruption with epidermal detachment. Pediatric patients less than 18 years old and pregnant patients were excluded. Data collected for each patient included the medication that precipitated the reaction; reaction type; age when the reaction occurred; current antibiotic therapy; indication for therapy; preferred antimicrobial agent; days of therapy on each agent used; positive, negative, or ambiguous PST result; recent antihistamine use; and any adverse events that occurred. Outcomes of the PST results, pharmacist interventions made after PST, and resulting cost savings to patients were all reported. Results: Among 31 patients tested, 27 were negative for penicillin allergy, 1 was positive for penicillin allergy, and 3 yielded an indeterminate test. Pharmacist recommendation to change therapy based on PST results was accepted in 13 of 15 patients where recommendations were made. Cost savings in antimicrobial therapy alone for patients who received PST was US $74.75 per day. Conclusion: Pharmacist-driven PST provided opportunities to clarify allergies, optimize antimicrobial therapy, and save antimicrobial therapy-related costs to patients.

272. Impact of Matrix-Assisted Laser Desorption Ionization Time-of-flight Mass Spectrometry (MALDI-TOF MS) on Time to Optimal Antimicrobial Therapy in Pediatric Patients with Positive Blood Cultures at Children’s Cancer Hospital-Egypt (CCHE-57357)

BackgroundThe clinical microbiology laboratory at CCHE-57357 implemented the MALDI-TOF MS for pathogen identification directly from positive blood cultures in 2016. Prior to that conventional method was used. The purpose of this study was to evaluate the impact of using the MALDI-TOF MS on the time to pathogen identification, time to administration of the optimal antimicrobial treatment and on the clinical outcomes for pediatric patients at CCHE-57357.MethodsThis was a retrospective, descriptive, observational study design. Data were collected for children admitted to CCHE-57357 with positive blood cultures identified by traditional culture method from July 1, 2015 to September 30, 2015 and by MALDI-TOF MS from July 1, 2016 to September 30, 2016. Outcome measures included time from reporting of a positive blood culture until organism identification and susceptibilities, time to optimal antimicrobial treatment, and clinical outcome across the two study periods (before and after the use of MALDI-TOF MS).ResultsA total of 172 positive blood cultures were included in the analysis: 64 before and 108 after the implementation of MALDI-TOF MS. The mean time to blood cultures positivity detected by BACTEC system was similar in both time periods, while the mean time to organism identification decreased significantly by 35% from 60 to 39 hours (P = 0.001) after the use of MALDI-TOF MS. Concurrently, the time to susceptibilities was significantly reduced by 30% from 82 to 57 hours (P = 0.001) and the time to starting optimal antimicrobial therapy was reduced significantly by 33% from 81 to 54 hours (P = 0.001). Optimal antimicrobial therapy was initiated within 72 hours from the time of blood culture inoculation in 37% of pediatric patients before and 76% after the use of MALDI-TOF MS (P = 0.01). Thirty-day all-cause mortality was lower after the use of MALDI-TOF, but the difference was not statistically significant (9.2% vs. 16.9%, P = 0.122).ConclusionThe study concluded that applying MALDI-TOF technology significantly reduced the time needed to pathogen identification and to initiate optimal antimicrobial therapy. This will eventually improve patient clinical outcomes, and reduce mortality in our immunocompromised pediatric population. Disclosures All authors: No reported disclosures.