Initiation Of Antimicrobial Therapy Research Articles

847. The Effect of Antimicrobial Administration on Blood Culture Positivity in Patients with Severe Manifestations of Sepsis

BackgroundCurrent guidelines recommend obtaining blood cultures prior to antimicrobial therapy in patients with sepsis. Administering antimicrobials immediately without waiting for blood cultures could potentially decrease time to treatment and improve outcomes, but it is unclear the degree to which this strategy impacts diagnostic yield.MethodsWe performed a patient-level, single-arm, diagnostic trial. Seven urban emergency departments affiliated with academic medical centers across Canada and the United States participated in the study. Adults ≥18 years of age presenting to the emergency department with evidence of severe manifestations of sepsis, including a systolic blood pressure <90 mmHg and/or a serum lactate ≥4 mmol/L were included. Study participants had 2 sets of blood cultures drawn prior to and immediately following antimicrobial administration. The primary outcome was the difference in blood culture pathogen recovery rates before and after administration of antimicrobial therapy.ResultsOf the 3,164 participants screened, 325 were included in the study (mean age, 65.6 years; 63.0% men) and had repeat blood cultures drawn after the initiation of antimicrobial therapy (median time of 70 minutes, IQR 50 to 110 minutes). Pre-antimicrobial blood cultures were positive for one or more microbial pathogens in 102/325 (31.4%) patients. Fifty-four participants (52.9%) had matching blood culture results after initiation of antimicrobial treatment. The absolute difference in pathogen recovery rates was 14.5% ([95% CI 8.0 to 21.0%]; P < 0.0001) between pre- and post-antimicrobial blood cultures. Results were consistent in an analysis of the per-protocol population (absolute difference, 13.3% [95% CI 6.1 to 20.4%]; P < 0.0001). Including the results of other microbiological cultures done as part of routine care, microbial pathogens were recovered in 69 of 102 (67.7%) participants (absolute difference, 10.2% [95% CI 3.4 to 16.8%]; P < 0.0001).ConclusionAmong patients with severe manifestations of sepsis, the administration of empiric antimicrobial therapy significantly reduces the yield of pathogen recovery when blood cultures are drawn shortly after treatment initiation. Disclosures All Authors: No reported Disclosures.

1348. Mycobacterium Chimera Infection Following Cardiac Surgery: A Review of a Large Cohort of Cases in the United States

BackgroundMycobacterium chimera (MC) is a nontuberculous mycobacterium associated with infections originating from heater-cooler devices following cardiac surgery globally from 2012 to 2016. Twenty-eight cases occurred within our health system in Southern California, the largest number of cases in the United States to date. We aim to summarize the clinical features, diagnosis, treatments, and outcomes of these cases.MethodsWe reviewed the electronic health records of 28 patients with identified MC infection who had index coronary artery bypass (CABG) and/or valve replacement surgery between 2014 and 2016. All diagnoses were confirmed by cultures speciated to MC by 16S partial DNA sequencing or Karius testing, except for one case. Patients were grouped by clinical presentation of disseminated disease (n = 18) or localized disease (n = 10). Treatment delay was calculated from the time of initial presentation to the start date of antibiotics and evaluation for surgical intervention.ResultsAll patients who underwent CABG alone (n = 5) developed localized sternal wound infections, whereas patients who had valve replacement surgery (n = 23) developed either localized or disseminated disease. Disseminated disease carried a mortality rate of 40% in those with surgical source control vs. 72% in patients who were not surgical candidates (OR 6.6, 95% CI 0.8–55). The mortality rate of patients with localized sternal wound infections was 11% after incision/drainage and sternal wire removal (n = 9). Delay of antimicrobial treatment greater than 6 months in all 28 patients was associated with a mortality rate of 54% compared with 35% in patients who started treatment within 6 months (OR 2.2, 95% CI 0.47–10.35). Overall mortality rate of patients with MC infection was 42%.ConclusionDisseminated MC infection should be considered early in at-risk patients presenting with constitutional symptoms. In this review of 27 confirmed and 1 probable case of MC infection, disseminated infection only occurred in patients who underwent valve surgery while localized disease occurred in patients who underwent CABG. Surgical source control with early initiation of antimicrobial therapy is associated with improved outcomes. Optimal duration of antimicrobial treatment is still unknown.Disclosures All authors: No reported disclosures.

ASSOCIATION OF 1,3-BETA-D-GLUCAN AND DEGREE OF HYPOXEMIA IN NON-HIV PNEUMOCYSTIS PNEUMONIA

SESSION TITLE: Outcomes of Respiratory Infections in the Immunocompromised Host SESSION TYPE: Original Investigations PRESENTED ON: 10/20/2019 2:15 PM - 3:15 PM PURPOSE: Pneumocystis jirovecii pneumonia (PCP) is a highly morbid respiratory infection that affects immune-suppressed hosts with and without HIV. Presence or absence of HIV impacts the degree of immune response observed. Non-HIV patients with PCP exhibit a greater degree of lung inflammation, despite lower Pneumocystis organism burden. Studies have examined the utility of 1,3-β-D glucan (BDG), a cellular component of Pneumocystis, as a diagnostic tool in PCP. The purpose of this study is to describe the association of BDG assay and degree of hypoxemia in non-HIV adults presenting with PCP. METHODS: This was a single-center, retrospective cohort study of non-HIV adults who presented with microbiologic-confirmed PCP at Mayo Clinic in Rochester, MN between 2011 and 2017. Patients were included if they had an available BDG concentration on PCP presentation prior to treatment initiation. The primary objective was to determine the relationship between BDG concentration and degree of hypoxemia at the time of PCP presentation. BDG concentrations were categorized as negative (500 pg/ml) based on the bounds of detection of the assay and the median observed. Wilcoxon rank sum test was used to compare PaO2/FiO2 (PF) and SaO2/FiO2 (SF) between the BDG groups at PCP presentation. RESULTS: The 38 included patients had a median (IQR) age of 65 (54, 72) years, 25 (66%) were male, and the most common immune-suppressive condition was hematologic malignancy (N = 27; 71%). BDG concentrations were negative in 7 (18%), mild positive in 8 (21%), moderate positive in 8 (21%), and strong positive in 15 (40%). Among the patients with available arterial blood gases for assessment (N = 24), the median PF ratio was 156 (103, 189). The median SF ratio was 223 (157, 320). Non-invasive positive pressure or mechanical ventilation was required in 9 (24%) cases. Compared to negative BDG, strong positive BDG concentrations were associated with worse PF (211 vs. 138, p = 0.043) and SF (332 vs. 195, p = 0.003) ratios. Compared to negative BDG, mild positive BDG concentrations were associated with worse SF ratios (332 vs. 241, p = 0.024). CONCLUSIONS: Among non-HIV patients presenting with PCP, higher pre-treatment BDG concentrations were associated with a greater degree of hypoxemia. CLINICAL IMPLICATIONS: PCP is on the rise among non-HIV immune-suppressed individuals and mortality rates are significant. With an association between higher BDG concentrations and lower PF and SF ratios, our study reveals a potential approach for prognosticating severity of respiratory failure at the time of PCP presentation. With lysis of Pneumocystis organisms on initiation of antimicrobial therapy, our study opens further investigations to explore the association of BDG and severity of hypoxemia over the course of PCP treatment. DISCLOSURES: Advisory Committee Member relationship with Fast Biomedical Please note: $1-$1000 Added 03/13/2019 by Erin Barreto, source=Web Response, value=Consulting fee No relevant relationships by Jason Barreto, source=Web Response No relevant relationships by Andrew Limper, source=Web Response No relevant relationships by Kristin Mara, source=Web Response No relevant relationships by Patrick Wieruszewski, source=Web Response No relevant relationships by Hemang Yadav, source=Web Response

Blood Culture Results Before and After Antimicrobial Administration in Patients With Severe Manifestations of Sepsis: A Diagnostic Study.

Administering antimicrobial agents before obtaining blood cultures could potentially decrease time to treatment and improve outcomes, but it is unclear how this strategy affects diagnostic sensitivity. To determine the sensitivity of blood cultures obtained shortly after initiation of antimicrobial therapy in patients with severe manifestations of sepsis. Patient-level, single-group, diagnostic study. (ClinicalTrials.gov: NCT01867905). 7 emergency departments in North America. Adults with severe manifestations of sepsis, including systolic blood pressure less than 90 mm Hg or a serum lactate level of 4 mmol/L or more. Blood cultures were obtained before and within 120 minutes after initiation of antimicrobial treatment. Sensitivity of blood cultures obtained after initiation of antimicrobial therapy. Of 3164 participants screened, 325 were included in the study (mean age, 65.6 years; 62.8% men) and had repeated blood cultures drawn after initiation of antimicrobial therapy (median time, 70 minutes [interquartile range, 50 to 110 minutes]). Preantimicrobial blood cultures were positive for 1 or more microbial pathogens in 102 of 325 (31.4%) patients. Postantimicrobial blood cultures were positive for 1 or more microbial pathogens in 63 of 325 (19.4%) patients. The absolute difference in the proportion of positive blood cultures between pre- and postantimicrobial testing was 12.0% (95% CI, 5.4% to 18.6%; P < 0.001). Sensitivity of postantimicrobial culture was 52.9% (CI, 42.8% to 62.9%). When the results of other microbiological cultures were included, microbial pathogens were found in 69 of 102 (67.6% [CI, 57.7% to 76.6%]) patients. Only a proportion of screened patients were recruited. Among patients with severe manifestations of sepsis, initiation of empirical antimicrobial therapy significantly reduces the sensitivity of blood cultures drawn shortly after treatment initiation. Vancouver Coastal Health, St. Paul's Hospital Foundation Emergency Department Support Fund, the Fonds de recherche Santé-Québec, and the Maricopa Medical Foundation.

Biomarkers in intensive care unit infections, friend or foe?

Antibiotic misuse is a crucial problem for critically ill patients. Biomarkers have emerged as tools to assist the clinician in antimicrobial therapy decisions among critically ill patients in intensive care units (ICU). They are useful for early identification of infection, timely initiation of antimicrobial therapy, and prompt evaluation of treatment course or duration. However, until now, an ideal biomarker has not yet been identified. The combination of procalcitonin (PCT), C-reactive protein (CPR) and other biomarkers may overcome their insufficiencies, with the high sensitivity of CRP compensating for the low sensitivity of PCT. Biomarkers could not predict antimicrobial resistance, and development of molecular diagnosis brings new challenges. The most important thing for the clinician is to understand the advantages and disadvantages of different methods so that to use them reasonably.

Spinal epidural abscess caused by Pasteurella multocida mimicking aortic dissection: a case report

BackgroundPasteurella multocida (P. multocida) forms part of the normal flora of many animals. Although it is a common causative agent of skin and soft tissue infection after an animal bite or scratch, in rare cases it can cause spinal infections in humans.Case presentationA 68-year-old immunocompetent woman presented with fever and sudden onset of severe back pain mimicking aortic dissection. No findings related to the pain were revealed on enhanced computed tomography or initial magnetic resonance imaging (MRI) of the spine. The patient was found to be bacteremic with P. multocida, although she had no apparent injury related to animal contact. Repeated evaluation by MRI with gadolinium-contrast established the diagnosis of spinal epidural abscess. The patient was cured by the rapid initiation of antimicrobial therapy without surgery.ConclusionsWe describe the successful treatment of an individual with a spinal epidural abscess due to P. multocida without surgery. P. multocida infections may occur as sudden presentations. Obtaining the patient history of recent animal contact is essential. Repeated MRI evaluation may be required when spinal infections are suspected. To the best of our knowledge, this is the first report which describes a case of spinal epidural abscess due to this organism.

Antibiotic use in critical illness.

To provide a review on the current use of antimicrobials with a discussion on the pharmacokinetic and pharmacodynamic profiles of antimicrobials in critically ill patients, the challenges of drug resistance, the use of diagnostic testing to direct therapy, and the selection of the most likely efficacious antimicrobial protocol. Patients in the intensive care unit often possess profound pathophysiologic changes that can complicate antimicrobial therapy. Although many antimicrobials have known pharmacodynamic profiles, critical illness can cause wide variations in their pharmacokinetics. The two principal factors affecting pharmacokinetics are volume of distribution and drug clearance. Understanding the interplay between critical illness, drug pharmacokinetics, and antimicrobial characteristics (ie, time-dependent vs concentration-dependent) may improve antimicrobial efficacy and patient outcome. Utilizing bacterial culture and susceptibility can aid in identifying drug resistant infections, selecting the most appropriate antimicrobials, and hindering the future development of drug resistance. Having a basic knowledge of antimicrobial function and how to use diagnostics to direct therapeutic treatment is paramount in managing this patient population. Diagnostic testing is not always available at the time of initiation of antimicrobial therapy, so empiric selections are often necessary. These empiric choices should be made based on the location of the infection and the most likely infecting bacteria. Studies have demonstrated the importance of moving away from a "one dose fits all" approach to antimicrobial therapy. Instead there has been a move toward an individualized approach that takes into consideration the pharmacokinetic and pharmacodynamic variabilities that can occur in critically ill patients.

Cost avoidance associated with clinical pharmacist presence in a medical intensive care unit

ObjectiveTo determine the clinical pharmacist‐generated cost avoidance and benefit‐cost ratio in a medical intensive care unit (MICU).MethodsAll accepted clinical pharmacist recommendations on a multidisciplinary, rounding service at an academic medical center over a 12‐month period were evaluated. Cost avoidance values from each intervention were determined using a systematic framework. Total cost avoidance was calculated by summing the cost avoidance for each general category. Average rates of cost avoidance per day and hour were calculated by dividing total cost avoidance by number of days and hours the clinical pharmacist provided care. Average interventions and cost avoidance per day and hour were calculated for weekday and call status. Differences between months, day of the week, and call status were evaluated using chi‐square goodness of fit tests.ResultsOver 12 months, 8866 clinical pharmacist‐recommended interventions were implemented, averaging 38.9 interventions per workday. The four most commonly accepted interventions were minor adverse drug event prevention (n = 4023, 45%), dosage adjustment: no continuous renal replacement therapy (n = 1162, 13%), antimicrobial therapy initiation and streamlining (n = 966, 11%), and antimicrobial pharmacokinetic evaluation (n = 777, 9%). All interventions resulted in a total cost avoidance of $3 270 178, averaging $14 731 per workday. Interventions per hour (P &lt; 0.001) and average cost avoidance per hour (P &lt; 0.001) differed significantly across workdays. For on‐call days compared with postcall days, there were a similar average number of interventions per hour (10.2 vs 9.8, P = 0.28) and average cost avoidance per hour ($3741 vs $3622, P = 0.47); the benefit‐cost ratio was 24.5:1.ConclusionsThe clinical pharmacist‐generated cost avoidance over a 12‐month period in the MICU was $3 270 178 and the benefit‐cost ratio was 24.5:1. Day of the week but no call status affected average cost avoidance. Employing a clinical pharmacist to be part of the multidisciplinary MICU team can reduce health care expenditures through cost avoidance.

Pertussis: The Identify, Isolate, Inform Tool Applied to a Re-emerging Respiratory Illness.

Pertussis, commonly referred to as “whooping cough,” is a highly contagious acute respiratory infection that has exhibited cyclical outbreaks throughout the last century. Although vaccines have provided some immunity, many populations, including infants and pregnant women, remain at risk for serious illness. Through the use of the novel “Identify, Isolate, Inform” (3I) tool, emergency department (ED) providers can readily recognize key symptoms of the disease and risk factors for exposure, thus curbing its transmission through early initiation of antimicrobial therapy and post-exposure prophylaxis. The three classic stages of pertussis include an initial catarrhal stage, characterized by nonspecific upper respiratory infection symptoms, which may advance to the paroxysmal stage, revealing the distinctive “whooping cough.” This cough can persist for weeks to months leading into the convalescent stage. Household contacts of patients with suspected pertussis or other asymptomatic, high-risk populations (infants, pregnant women in their third trimester, and childcare workers) may benefit from post-exposure prophylactic therapy. The Pertussis 3I tool can also alert healthcare professionals to the proper respiratory droplet precautions during contact with a symptomatic patient, as well as isolation practices until antimicrobial treatment is in progress. ED personnel should then inform local public health departments of any suspected cases. All of these actions will ultimately aid public health in controlling the incidence of pertussis cases, thus ensuring the protection of the general public from this re-emerging respiratory illness.

Causes and Predictors of Early Mortality in HIV-Positive and HIV-Negative Patients with Diffuse Large B-Cell Lymphoma

INTRODUCTION:There is a lack of data on early mortality in aggressive lymphomas, particularly HIV-related lymphomas. Patients who present with advanced disease and poor performance status are at a higher risk of adverse outcomes and are not offered clinical trial enrollment. Factors that may contribute to early mortality have not been delineated. In this retrospective analysis, we sought to identify causes and predictors of early mortality, occurring within 180 days of index diagnosis, in patients with HIV-positive and negative DLBCL, at an academic medical center.METHODS:We reviewed an electronic database to identify patients with a diagnosis of HIV-related DLBCL, treated at our center between January 1, 2005 and December 31, 2017. We further identified patients with non-HIV positive DLBCL diagnosed from January 1, 2015 to December 31, 2017. Data on patient demographics, clinical outcomes and treatment was collected. We defined early mortality as those patients who died within 180 days of diagnosis.RESULTS:HIV-NEGATIVE DLBCL: There were 103 HIV-negative patients with DLBCL, with a mean age of 65 years. N=17 (16.5%) patients expired within 180 days of diagnosis. In univariate analysis, factors predicting increased risk of mortality included poor ECOG performance status (PS) 3-4, presence of B-symptoms and higher international prognostic index (IPI) scores (Table 1). In multivariate analysis, poor PS (HR 4.86, p<0.03) and B-symptoms (HR 5.9, p<0.02) remained significant predictors of early mortality. Age, cell of origin and Hepatitis B/C positivity were not found to be predictive. The leading cause of death in the first 180 days was sepsis, attributing for 53% of mortality (Figure 1). Other commonly identified causes included progressive disease (23%), tumor lysis and cardiac complications (12%).HIV-POSITIVE DLBCL: We identified 82 patients with HIV-positive DLBCL and divided patients into Cohort A (N=25) patients who expired within 180 days and Cohort B (N=57), patients who were alive beyond 180 days. 9 patients died within the first 30 days, 20 patients within 90 days and 25 patients within 180 days of index diagnosis. Both groups predominantly consisted of African-Americans with advanced stage DLBCL with a mean age of 53 and 48 years respectively (p=0.02). In univariate analysis, more patients in Cohort A had Stage 3-4 DLBCL (100% vs. 86%), poorer ECOG PS of 3-4 (52% vs. 7%), higher IPI scores (56% vs. 11%), lower CD4 counts (median of 70 cells/uL vs. 140 cells/uL) and higher LDH (544 U/L vs. 270 U/L). In multivariate analysis, we found that poor ECOG PS (HR 2.4, p<0.0001), higher LDH (HR 1, p<0.008) and older age (HR 1.07, p<0.023) were associated with an increased risk of mortality at 180 days. The leading causes of death within 180 days were progressive disease in 48%, and sepsis in 32% of patients.We wanted to examine whether the time period of diagnosis affected mortality from HIV-related DLBCL in patients. Group 1 patients were diagnosed from January 2005 to December 2010 (N=20) and Group 2 from January 2011 to December 2017 (N=29). We found that in Group 1, 50% of patients died from progressive disease and 15% of patients died from an acute event. Meanwhile, in Group 2, 38% of patients died from progressive disease, and 52% died from an acute event. Sepsis was the most common acute event in both groups.CONCLUSION:Preventing early mortality in aggressive lymphomas is crucial to improving overall survival. For patients with non-HIV related DLBCL, we found poor ECOG PS and presence of B-symptoms to be predictors of early mortality. In patients with HIV-positive DLBCL, poor ECOG PS, higher LDH and older age were contributing factors. The leading cause of death in both HIV-positive and HIV-negative patients (2011- 2017) was sepsis followed by progressive disease at 180 days after diagnosis.Although sepsis is a major factor contributing to early mortality and morbidity, it is preventable with prophylaxis against opportunistic infections. In order to decrease sepsis related mortality, we propose early initiation of antimicrobial therapy in patients at high risk based on independent clinical variables identified in this study. A prospective study preventing sepsis in high risk patients is warranted to decrease early mortality in patients with aggressive lymphoma. [Display omitted] DisclosuresJanakiram:Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

Risk Factors for Delayed Antimicrobial Treatment in Febrile Children with Urinary Tract Infections

To identify factors associated with delayed antimicrobial treatment in febrile children with urinary tract infection (UTI). We reviewed data from 802 children with UTI enrolled in 2 previously conducted prospective studies (Randomized Intervention for Children with Vesicoureteral Reflux and Careful Urinary Tract Infection Evaluation) and extracted data on possible predictors of delayed treatment including age, sex, history of UTI, ethnicity, race, primary caregiver's education level, insurance, and income. We used univariate and multivariable analyses to investigate the relationship between these predictors and treatment delay. We included 660 febrile patients with a mean age of 17.0 months old. Older age and commercial insurance were associated with delayed treatment on univariate analysis. Compared with younger children, treatment was delayed by an average of 26.2 hours in children ≥12 months of age. This relationship remained significant on multivariable analysis. Treatment also was delayed by an average of 12.6 hours in patients with commercial insurance. Race, ethnicity, primary caregiver's education level, and income were not associated with delayed treatment. Older age was a consistent predictor of delayed antimicrobial treatment. Delays in the initiation of antimicrobial therapy for UTI has previously been associated with renal scarring. Educating parents with older children regarding the management of fever as well as providers regarding prompt evaluation and management may help to reduce renal scarring.

Genitourinary Tract Infection Due to Mycobacterium avium intracellulare Complex Infection in Pretransplant Setting With Recurrence Following Transplant: A Case Report

Genitourinary (GU) tract infection with Mycobacterium avium intracellulare complex (MAI) is very rare and, to our knowledge, has never been reported in the solid organ transplant literature. Case DescriptionA 61-year-old Somali-born woman had a history of liver cirrhosis due to chronic hepatitis C infection. She was diagnosed as having and treated for latent tuberculosis infection and GU tract infection due to MAI. She received a total of 17 months antimycobacterial therapy consisting of azithromycin, ethambutol, and moxifloxacin. Within 5 months of the initiation of antimicrobial therapy, there was documented sterilization of urine mycobacterial cultures. Liver and kidney transplant was performed 3 months after finishing the treatment course. One year following transplant, GU tract infection due to MAI recurred. She declined further diagnostic testing as well as mycobacterial therapy. She died 15 months following transplant for reasons not related to infections. ConclusionThe treatment of MAI infection in solid organ transplant candidates and recipients is challenging, and the duration of therapy in this population is not known. The recurrence of infection following transplant in this case may argue in favor of a duration that extends beyond the date of transplant. The combination of a fluoroquinolone and ethambutol may successfully prevent reactivation of tuberculosis in patients with history of latent tuberculosis infection and deserves further evaluation.

Workup and Management of Native and Prosthetic Valve Endocarditis.

Infective endocarditis (IE) is associated with significant serious adverse outcomes including death. IE usually presents with diverse clinical picture and syndromic diagnoses including heart failure, stroke, and peripheral embolization. Given variable, vague, and syndromic presentations, the diagnosis of IE may be delayed for days to weeks. Maintaining a high index of suspicion among clinicians is the key to early recognition of the disease and prompt initiation of antimicrobial therapy to prevent IE-associated mortality and morbidity. Blood culture and echocardiography remain essential tools in the diagnosis of infective endocarditis. However, advances in molecular techniques, serology testing, computed tomography scan, and nuclear medicine have led to growth in the available tools that may aid in early diagnosis of infective endocarditis. Antimicrobial agents are the mainstay of IE therapy; however, as many as 50% of endocarditis cases will undergo valve surgery, even on an urgent or emergent basis.

Blood culture indications in critically ill neonates: a multicenter prospective cohort study

Center heterogeneity in sampling practice is substantial. Optimizing sampling practice can be recommended. What is Known: • Blood culture test is a common diagnostic procedure in critically-ill newborns. • A low threshold for sampling and antimicrobial therapy initiation is accepted. What is New: • Variability in blood culture practice was assessed between 3 neonatal intensive care units by the registration of sampling frequencies, clinical indications, and antimicrobial therapy initiation.

Automated monitoring compared to standard care for the early detection of sepsis in critically ill patients.

Automated monitoring compared to standard care for the early detection of sepsis in critically ill patients.

Clinical Impact of a Multiplex Gastrointestinal Polymerase Chain Reaction Panel in Patients With Acute Gastroenteritis

Molecular syndromic diagnostic panels can enhance pathogen identification in the approximately 2-4 billion episodes of acute gastroenteritis that occur annually worldwide. However, the clinical utility of these panels has not been established. We conducted a prospective, multi-center study to investigate the impact of the BioFire FilmArray Gastrointestinal polymerase chain reaction panel on clinical diagnosis and decision-making, and compared the clinical acuity of patients with positive results obtained exclusively with the FilmArray with those detected by conventional stool culture. A total of 1887 consecutive fecal specimens were tested in parallel by FilmArray and stool culture. Laboratory and medical records were reviewed to determine rates of detection, turnaround times, clinical features, and the nature and timing of clinical decisions. FilmArray detected pathogens in 35.3% of specimens, compared to 6.0% for culture. Median time from collection to result was 18 hours for FilmArray and 47 hours for culture. Median time from collection to initiation of antimicrobial therapy was 22 hours for FilmArray and 72 hours for culture. Patients diagnosed by FilmArray were more likely to receive targeted rather than empirical therapy, compared to those diagnosed by culture (P = .0148). Positive Shiga-like toxin-producing E. coli results were reported 47 hours faster with FilmArray and facilitated discontinuation of empirical antimicrobials. Patients diagnosed exclusively by FilmArray had clinical characteristics similar to those identified by culture. FilmArray markedly improved clinical sensitivity in patients with acute diarrhea, identified cases with clinical acuity comparable to those identified by culture, and enabled clinicians to make more timely and targeted therapeutic decisions.

Rationele antimicrobiële therapie voor sepsis bij runderen in het licht van de nieuwe wetgeving over kritisch belangrijke antibiotica

Sepsis is een levensbedreigende aandoening bij rundvee, net zoals bij de mens. Het snel toedienen van een breedspectrum-, bactericide antibioticum via intraveneuze weg is cruciaal voor een succesvolle behandeling van sepsis. De nieuwe wetgeving limiteert echter het gebruik van de kritisch belangrijke fluoroquinolonen en cefalosporinen bij voedselproducerende dieren. Deze antimicrobiële middelen worden als zeer effectief ervaren voor de behandeling van sepsis en werden vroeger dan ook veelvuldig ingezet voor deze indicatie. Het doel van dit artikel is een overzicht te geven van de huidige kennis over sepsis bij runderen om praktijkdierenartsen te sturen in hun beslissingsproces voor de behandeling van sepsis. De incidentie van sepsis bij rundvee wordt hoogstwaarschijnlijk ernstig onderschat. De ziekte werd vrijwel niet onderzocht bij runderen, wat het opstellen van speciesspecifieke richtlijnen sterk bemoeilijkt. De diagnose van sepsis door middel van bloedonderzoek is met de huidige laboratoriumtechnologie voldoende accuraat. Mogelijke hinderpalen voor een meer veralgemeende toepassing zijn de minder hygiënische stalomgeving en de beperkte beschikbaarheid van aangepaste apparatuur in veterinaire labo’s, maar deze lijken niet onoverkomelijk. Ernstige sepsis en septische shock zijn mogelijk de enige indicaties die in aanmerking komen voor het hoogdringendheidscriterium zoals in de wetgeving weergegeven, maar het is belangrijk in te zien dat er ook antimicrobiële behandelingen met niet kritisch belangrijke moleculen bestaan met een mogelijk gelijkaardige effectiviteit.

Orbital apex syndrome: An unusual complication of invasive mucormycosis

Orbital apex syndrome is a rare manifestation of invasive mucormycosis. We report a case of orbital apex syndrome in a diabetic patient which not only posed a diagnostic challenge but also required a multidisciplinary approach in treatment and management. Prompt imaging followed by early initiation of antimicrobial therapy along with timely surgical intervention were integral in preventing further complications and reducing mortality. However, despite these measures, the patient sustained partial vision loss due to endophthalmitis as a complication.

BACTERIOLOGICAL PROFILE AND ANTIBIOTIC SENSITIVITY PATTERN OF HOSPITALACQUIRED SEPTICEMIA IN A TERTIARY CARE HOSPITAL IN NORTH EAST INDIA

Objective: The objective of this study was to determine the bacterial agents responsible for hospital acquired septicaemia and to determine the antibiotic sensitivity profile of the bacterial isolates.Methods: Three hundred fifty hospitalized clinically suspect septicaemia cases were included in this cross sectional observational study during a period of one year. Blood samples were collected with aseptic precautions for culture following universal precautions. Anti-microbial susceptibility test of the bacterial isolates was performed according to Clinical and Laboratory Standards Institute (CLSI, USA) guidelines. Results: Over two-thirds of cultures showed gram positive organism. The most frequently identified Gram positive bacteria were coagulase negative staphylococci and Staphylococcus aureus. Among gram negative bacteria Escherichia coli, Klebsiella spp and Salmonella typhi were isolated. In our study, coagulase negative staphylococci showed maximum resistance to penicillin and erythromycin. Enterobactereciae had maximum sensitivity to carbapenems, tigecycline and aminoglycosides.Conclusion: Gram positive pathogens predominated in the blood stream infections. Résistance to fluoroquinolones, especially in Gram negative bacteria was significantly high. Therefore, rapid microbiological diagnosis and the determinants of antimicrobial susceptibility become relevant for early initiation of antimicrobial therapy.

Oh Rats!! An Unusual Case of Jaundice Due to Leptospirosis

Conjugated hyperbilirubinemia in the absence of hepatocellular injury requires investigation of unique pathologic entities. Leptospirosis is a rare zoonotic infection which can result in conjugated hyperbilirubinemia and acute kidney injury. Humans are infected via rodent-urine contaminated water or soil. Incidence of Leptospirosis in the United States is extremely rare with estimates of only 100 cases annually, a majority of which are reported in Hawaii and California. Other complications include thrombocytopenia, ARDS, pulmonary hemorrhage and myocarditis. A 43 year-old Caucasian man residing in Detroit, Michigan presented with abdominal pain for five days. Associated symptoms included subjective fevers, generalized weakness and jaundice. He reported living with five dogs in a rat-infested home. He denied any recent travel or sick contacts. Examination revealed a jaundiced, dishevelled man with scleral icterus and marked conjunctival erythema without exudate (Figure 1). Lab work revealed leukocytosis, pyuria and conjugated hyperbilirubinemia, but unremarkable transaminases. The patient deteriorated within the next 12 hours, requiring transfer to the intensive care unit, mechanical ventilation and vasopressor support. Chest radiography revealed bilateral patchy infiltrates suggestive of ARDS (Figure 2). Ultrasound and CT scan of the abdomen were unremarkable. Leptospirosis IgM antibody was negative. The conjugated bilirubin continued to rise to a plateau of 22.8mg/dL. Molecular testing with RT-PCR revealed Leptospira DNA. The patient was treated with ceftriaxone leading to resolution of acute kidney injury and hyperbilirubinemia (Figure 3). Although incidence of Leptospirosis is extremely rare in the Midwestern United States, it must be considered in cases of conjugated hyperbilirubinemia and renal dysfunction. Hyperbilirubinemia is postulated to result from endothelial damage to hepatic capillaries and hyperplasia of Kupffer cells causing intrahepatic cholestasis. Important clues may include conjunctival suffusion (Figure 1) or rodent-infested living conditions. A Jarisch-Haerxheimer reaction (fever, rigors and hypotension) may occur after initiation of antibiotics as seen in this case. Molecular testing (RT-PCR) is the test of choice as serologic testing can be unrevealing in the early stages of infection. High index of suspicion and initiation of antimicrobial therapy are essential in avoiding the complications of this devastating zoonotic disease.Figure: Conjunctival suffusion and scleral icterus involving both eyes.Figure: Chest radiography unremarkable on presentation (day 0), however, repeat imaging on day 2 shows extensive diffuse airspace disease. Given worsening following initiation of antibiotics, this is consistent with a Jarisch-Haerxheimer reaction in retrospect.Figure: Graphical representation of the hospital course correlated with white blood cell count and bilirubin levels.