Administration Of Antimicrobial Therapy Research Articles

To treat or not to treat: Assessing the role of anti-enterococcal therapy for intra-abdominal infections in patients with cancer.

The clinical significance of enterococci in intra-abdominal infections, particularly those caused by multiple organisms, remains unclear. There are no definitive guidelines regarding the use of empiric therapy with antimicrobial agents targeting enterococci. In this study, we evaluated the impact of the initial antimicrobial therapy administration of anti-enterococcal agents on the treatment of intra-abdominal infections in patients with cancer in whom enterococci were isolated from ascitic fluid cultures. This retrospective study was conducted at Shizuoka Cancer Center between January 1, 2014, and December 31, 2020, on all adult patients with cancer with enterococci in their ascitic fluid cultures. The primary outcome was all-cause mortality, and the secondary outcomes were composite outcomes consisting of three components (mortality, recurrence, and treatment failure) and the risk factors associated with all-cause mortality and composite outcomes. In total, 103 patients were included: 61 received treatment covering enterococci, and 42 did not. The mortality rates did not differ significantly between the treated and untreated groups (treated: 8/61 [13.1%]; untreated: 5/42 [11.9%]; p = 1.00). Additionally, no significant difference was observed between the groups in terms of composite outcomes (treated group: 11/61 [18.0%]; untreated group: 9/42 [21.4%]; p = 0.80). Multivariate analysis showed that performance status (PS2-4; p < 0.0001) was an independent risk factor for mortality. The composite outcome was also significantly higher for PS2-4 (p = 0.007). Anti-enterococcal treatment was not associated with mortality or the composite outcome. In patients with cancer and intra-abdominal infections caused by enterococci, anti-enterococcal therapy was not associated with prognosis, whereas PS2 or higher was associated with prognosis. The results of this study suggest that the initial routine administration of anti-enterococcal agents for intra-abdominal infections may not be essential for all patients with cancer. To substantiate these findings, validation by a prospective randomized trial is warranted.

Applicability of an in-house extraction protocol in a Bruker Biotyper matrix-assisted laser desorption/ionization time-of-flight mass spectrometry system for the identification of Streptococcus agalactiae from broth-enriched vaginal/rectal swab specimens.

Early laboratory identification of group B Streptococcus (GBS, Streptococcus agalactiae) in the birth canal of pregnant women is critical for prompt administration of antimicrobial therapy and may further reduce the mortality rate due to GBS neonatal infection. A total of 164 vaginal/rectal swab specimens collected from pregnant women at 35-37 weeks of gestation were screened for GBS vaginal colonization. The matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS, Bruker Biotyper, Bruker Daltonik GmbH, Bremen, Germany) system was used to detect GBS from Carrot broth and LIM broth enrichment using an in-house extraction protocol. The results were compared to those by conventional broth-enriched culture/identification methods as the gold standard. BD MAX™ GBS assay (Becton Dickinson, Sparks, MD, USA) was also performed for Carrot broth-enriched specimen. Discordant results were investigated using the GeneXpert® GBS PCR assay (Cepheid Inc., Sunnyvale, CA, USA). Using the extraction protocol, 33 (20.1%) of the 164 specimens were positive in Carrot broth, and 19 (11.6%) were positive in LIM broth. Using the culture protocol, 38 (23.2%) samples in Carrot broth and 35 (21.3%) in LIM broth were positive. The sensitivity, specificity, and positive and negative predictive values using the extraction protocol in Carrot broth and LIM broth compared to the gold standard conventional culture/identification method were 86.8% and 50.0%, 100% and 100%, 100% and 100%, and 96.2% and 86.9%, respectively. The extraction protocol with MALDI-TOF MS from Carrot broth-enriched samples provides a more rapid turnaround time, lower cost, and acceptable sensitivity and specificity to correctly identify pathogens when compared to conventional culture/identification methods.

QSOFA does not predict bacteremia in patients with severe manifestations of sepsis.

Bloodstream infections in septic patients may be missed due to preceding antibiotic therapy prior to obtaining blood cultures. We leveraged the FABLED cohort study to determine if the quick Sequential Organ Failure Assessment (qSOFA) score could reliably identify patients at higher risk of bacteremia in patients who may have false negative blood cultures due to previously administered antibiotic therapy. We conducted a multi-centre diagnostic study among adult patients with severe manifestations of sepsis. Patients were enrolled in one of seven participating centres between November 2013 and September 2018. All patients from the FABLED cohort had two sets of blood cultures drawn prior to the administration of antimicrobial therapy, as well as additional blood cultures within 4 hours of treatment initiation. Participants were categorized according to qSOFA score, with a score ≥2 being considered positive. Among 325 patients with severe manifestations of sepsis, a positive qSOFA score (defined as a score ≥2) on admission was 58% sensitive (95% CI 48% to 67%) and 41% specific (95% CI 34% to 48%) for predicting bacteremia. Among patients with negative post-antimicrobial blood cultures, a positive qSOFA score was 57% sensitive (95% CI 42% to 70%) and 42% specific (95% CI 35% to 49%) to detect patients who were originally bacteremic prior to the initiation of therapy. Our results suggest that the qSOFA score cannot be used to identify patients at risk for occult bacteremia due to the administration of antibiotics pre-blood culture.

Incidence, characteristics and risk factors of hypofibrinogenemia associated with tigecycline: A multicenter retrospective study in China.

Background: Tigecycline was recently found to cause coagulation disorders, especially hypofibrinogenemia, which may interfere with the administration of antimicrobial therapy. This study aimed to investigate the incidence and clinical characteristics of and risk factors for tigecycline-associated hypofibrinogenemia. Methods: In this multicenter retrospective study, patients receiving tigecycline or imipenem–cilastatin to treat Gram-negative bacterial infections in nine Chinese tertiary hospitals between January 2020 and December 2020 were enrolled. Baseline data and coagulation variables were compared using cohort and case–control studies. Results: Totals of 485 patients treated with tigecycline and 490 patients treated with imipenem–cilastatin were included in this study. Compared with imipenem–cilastatin, tigecycline was associated with reduced fibrinogen and prolonged activated partial thromboplastin time and prothrombin time (all p < 0.001), with the most remarkable change in fibrinogen (down by 48.0%). The incidence of hypofibrinogenemia in patients treated with tigecycline was >50%, with propensity score-matched analysis or not. The relative risk of hypofibrinogenemia with tigecycline versus imipenem–cilastatin was 2.947 (95% CI: 2.151–4.039) at baseline balance. Tigecycline-associated hypofibrinogenemia led to a higher incidence (12.1%) of bleeding events. However, none of supplemental therapies after withdrawal had an effect on the normalization of fibrinogen levels. The risk factors for tigecycline-associated hypofibrinogenemia were treatment duration ≥6 days (odds ratio [OR] 5.214, 95% confidence interval [CI] 2.957–9.191, p < 0.001), baseline fibrinogen <4 g/L (OR 4.625, 95% CI 2.911–7.346, p < 0.001), cumulative dose ≥1,000 mg (OR 2.637, 95% CI 1.439–4.832, p = 0.002), receiving CRRT (OR 2.436, 95% CI 1.179–5.031, p = 0.016), baseline PT > 14 s (OR 2.110, 95% CI 1.317–3.380, p = 0.002) and baseline total bilirubin >21 μmol/L (OR 1.867, 95% CI 1.107–3.147, p = 0.019), while the protective factor was skin and soft tissue infection (OR 0.110, 95% CI 0.026–0.473, p = 0.003). Conclusion: The clinical characteristics of and risk factors for tigecycline-associated hypofibrinogenemia identified in this study can offer practical reference for the clinical management of patients.

Role of the T2Dx magnetic resonance assay in patients with suspected bloodstream infection: a single-centre real-world experience

BackgroundT2Dx was approved by the US Food and Drug Administration for the rapid detection of a modified panel of ESKAPE bacterial species or Candida spp. causing bloodstream infection (BSI).Patients and methodsWe performed a retrospective, observational study from January 1, 2018 to December 31, 2019 of all hospitalised patients with suspected BSI who underwent assessment using T2Dx in addition to standard blood culture (BC). T2-positive patients (cases) were compared to a matched group of patients with BSI documented only by BC (1:2 ratio) to investigate the possible impact of T2Dx on the appropriateness of empirical antimicrobial therapy and 21-day mortality.ResultsIn total, 78 T2Dx-analysed samples (49 patients) were analysed. The T2Dx assay result was positive for18 patients and negative for 31 patients. The concordance rates of the T2Bacteria Panel and T2Candida Panel results with those of standard BC were 74.4% and 91.4%, respectively. In the matched analysis, inappropriate empiric antimicrobial therapy administration was significantly less frequent in cases than in comparators (5.5% vs. 38.8%). The 21-day mortality rate was twofold lower in cases than in comparators (22.2% vs. 44.4%), although the difference was not significant. No other analysed variables were significantly different between the two groups.ConclusionsThis study illustrated that T2Dx might be associated with an increase in the appropriateness of empiric antimicrobial therapy in patients with BSI. Further studies are needed to evaluate whether the T2Dx assay can improve patient outcomes.

Prognostic Effects of Delayed Administration of Antimicrobial Therapy in Older Persons Experiencing Bacteremia With or Without Initial Sepsis Presentations.

To investigate the prognostic effects of delayed administration of appropriate antimicrobial therapy (AAT) in older persons experiencing bacteremia with and without initial sepsis syndrome, respectively. A 4-year multicenter cohort study. Older people (≥65years of age) with community-onset bacteremia in the emergency department (ED) of 3 participating hospitals. Clinical data were retrospectively collected and causative microorganisms were prospectively collected for susceptibilities to determine the period of delayed AAT for each bacteremia episode. Sepsis was defined based on the Sepsis-3 criteria. A multivariable regression model was used to investigate the prognostic effects of delayed AAT, after adjusting independent determinants of 30-day mortality. Of the total 2357 patients, their median (interquartile range) age was 78 (72-84) years and septic patients accounted for 48.4% (1140 patients) of the overall patients. Compared with nonseptic patients, septic individuals exhibited the shorter period of delayed AAT (median, 2.0 vs 2.5hours; P < .001), longer hospitalization (median, 11 vs 9days; P < .001), and higher crude mortality rates at 15 (28.9% vs 2.1%; P < .001) and 30days (34.6% vs 4.0%; P < .001). In multivariable regression analyses, each hour of delayed AAT resulted in average increases in the 30-day crude mortality rates of 0.38% [adjusted odds ratio (AOR) 1.0038; P < .001), 0.42% (AOR 1.0042; P < .001), and 0.31% (AOR 1.0031; P= .04) among overall, septic, and nonseptic patients, respectively. For older persons with community-onset bacteremia, irrespective of whether or not patients experiencing initial sepsis presentations, the prognostic impacts of delayed AAT have been evidenced. Notably, because of the longer period of delayed AAT in patients without fulfilling the Sepsis-3, adopting a stricter sepsis definition and/or early bacteremia predictor to avoid delayed AAT and unfavorable prognoses in patients with bacteremia is necessary.

Analysis of antibiotic prescriptions in patients with community-acquired pneumonia in clinical practice

Objective. To analyze new strategies for the treatment of community-acquired pneumonia (CAP) by age and assess treatment efficacy by age category based on real world data. Materials and Methods. A total of 612 patients (medical charts) with CAP treated in 3 hospitals during the 2017–2019 were included in the retrospective pharmacoepidemiological study. A retrospective analysis of antimicrobial therapy (AMT) administration in the treatment of CAP was performed. Results. Duration of hospital stay in CAP patients of young age was 10% shorter than in patients of any other age category. The least frequency (19.6%) of antibiotic combination administration as initial empiric therapy was found in patients of young age. There were no significant differences in frequency of initial AMT administration between age groups. Ceftriaxone, cefepime and cefoperazone were the most common antimicrobials used as monotherapy in all age groups. Ceftriaxone with azithromycin combination was the most common (42%) initial combination therapy in all age groups. The highest number (27) of various antibiotic combinations was administered to old patients, and the lowest number (16) – to young patients. Efficacy of initial AMT was similar between elderly and old patients. Overall efficacy of initial AMT in patients with non-severe CAP and severe CAP was 54% and 50%, respectively. Analysis of antimicrobial treatment of CAP in real practice and its compliance with the current clinical guidelines showed cephalosporin plus macrolide to be a predominant antibiotic combination (83%). Conclusions. Antibiotic combination administration was found to be common in patients with non-severe CAP, whereas initial monotherapy was administered to severe CAP patients. Antibiotic prescription pattern in patient of young age was different from that in any other age groups. CAP had a less severe course in young patients as evidenced by shorter duration of hospital stay, more frequent monotherapy administration and higher efficacy of initial AMT compared to other age categories. There were no prescriptions of the recommended fifth generation cephalosporin (ceftaroline fosamil).

Triage guideline for immunocompromised children with fever in an emergency centre in Ethiopia.

Fever in children with neutropenia often portends life-threatening bacteremia that may be ameliorated with early recognition and the rapid administration of antimicrobial therapy. Studies demonstrating this effect have been done in resource-endowed countries, but not in resource-limited settings. We attempted to decrease the time to antibiotics in patients with fever and neutropenia presenting to a paediatric emergency centre at a tertiary care referral hospital in Ethiopia. In 3 phases we performed baseline data collection, instituted triaging and treatment guidelines, and provided antibiotics. We tracked a variety of outcomes, most importantly time from arrival to initiation of antibiotics. While this time was reduced during the guideline institution phase of our intervention, time reductions were inconsistent and not sustained. This was likely due to competing clinical priorities among providers caring for a high volume of ill children. While in the U.S., fever and neutropenia is easy to prioritise within the paediatric emergency centre, future quality improvement measures in this setting may have a greater benefit on critical presentations such as shock or respiratory failure. Alternative strategies geared towards general efficiency improvement and teamwork, rather than focusing on one patient group may be a higher yield approach for improving care in this paediatric emergency centre.

Peripherally inserted central venous catheter placed and maintained by a dedicated nursing team for the administration of antimicrobial therapy vs. another type of catheter: a retrospective case–control study

IntroductionData concerning the use of peripherally inserted central catheters (PICC) for the administration of intravenous (IV) antimicrobials in the acute care setting is scarce. MethodsWe performed a single-center retrospective case–control study (1:1). Case subjects were defined as patients who received IV antimicrobial treatment through a PICC line placed and maintained by specifically trained nurses (PICC group). Control subjects were defined as patients who received antimicrobial therapy by a peripheral or a central venous catheter (CVC) (control group). Control subjects were matched by type of antimicrobial, causative microorganism of the infection that was being treated and duration of treatment. An event leading to undesired catheter removal (ELUCR) was defined as any circumstance which lead to the removal of the indwelling catheter other than the completion of the scheduled course of antimicrobial therapy. ResultsThe study included 50 patients in each group. The total follow-up time was 1376 catheter-days for the PICC group and 1362 catheter-days for the control group. We observed a significantly lower incidence of ELUCR in the PICC group (0.2 versus 7.7 events per 100 catheter-days; P<0.001). When the incidence of ELUCR was analyzed according to the duration of indwelling catheterisation for each type of catheter (divided into one-week intervals), differences between both groups were also significant (P-values≤0.001 for the first three weeks of treatment). During the second week of IV treatment, only one patient in the PICC group (2.1%) developed an ELUCR compared to 19 (38.8%) in the control group (P<0.001). ConclusionsA PICC placed and maintained by a dedicated nursing team is an excellent alternative to peripheral venous catheters or CVCs for administrating antimicrobial therapy for both short and long periods of treatment.

Correlation of intraoperative donor duodenal-segment swab cultures with the subsequent occurrence of surgical site infections in kidney and pancreas transplant recipients.

Pancreas transplantation is employed for the treatment of type I diabetes mellitus. It is postulated that surgical site infection (SSI), particularly organ-space infections, after pancreas transplantation may arise from microbial contamination arising from the donor duodenal segment. Therefore, some centers have adopted the practice of culturing the donor duodenal segment and subsequently administering antimicrobial therapy to the recipient directed at the microorganisms isolated to prevent SSI. In this retrospective cohort study, we evaluated the correlation between positive donor duodenal-segment cultures and SSIs in the recipients. Data were recorded and analyzed to assess the correlation of the organisms isolated in the donor duodenal cultures with those producing SSI in the recipients. We evaluated 379 consecutive pancreas transplant recipients from January 2000 to December 2015. Donor duodenal swab cultures were performed at the time of pancreas transplantation, and 206 (54.3%) were positive. SSIs occurred in 51 of the 206 recipients (24.8%) with positive duodenal-segment cultures and in 41 of 173 individuals (23.7%) with negative cultures (P = .81; r = 0.00). Notably, deep and organ-space SSIs were observed in 27 of 206 of the positive duodenal culture groups (13.1%) versus 29 of 173 of the negative duodenal culture groups (16.8%; P = 0.31; r = -0.059). No differences were detected in the pathogens producing SSIs between the group with a positive duodenal swab versus the group with a negative swab. Microorganisms producing SSIs matched those found in the positive donor duodenal cultures in only 15 patients (7.8%). Although positive cultures from the donor duodenal segment prompted the administration of antimicrobial therapy in the recipient directed against the pathogen isolated, this practice did not reduce SSIs compared with those transplant recipients with culture-negative duodenal swabs. In addition, the organisms isolated from the donor duodenal segment were not predictive of subsequent SSI.

Early sepsis markers in patients admitted to intensive care unit with moderate-to-severe diabetic ketoacidosis

BackgroundBacterial infections are frequent triggers for diabetic ketoacidosis. In this context, delayed antibiotic treatment is associated with increased morbidity and mortality. Unnecessary administration of antimicrobial therapy might however, also negatively impact the prognosis. The usefulness of sepsis markers in diabetic ketoacidosis has not been assessed. Thus, we sought to investigate diagnostic performances of clinical and biological sepsis markers during diabetic ketoacidosis.MethodsIn this monocentric retrospective cohort study, all consecutive episodes of diabetic ketoacidosis (defined as pH ≤ 7.25, glycaemia > 300 mg/dL and presence of ketones) admitted in intensive care unit were included. A proven bacterial infection was defined as bacteriological documentation on any bacterial sample. Clinical (presence of fever: temperature > 38 °C and presence of hypothermia: temperature < 36 °C) and biological markers (whole blood count, neutrophils count, neutrophils-to-lymphocytes count ratio and procalcitonin), recorded at admission, were compared according to the presence or absence of a proven bacterial infection.ResultsBetween 2011 and 2018, among 134 episodes of diabetic ketoacidosis, 102 were included (91 patients). Twenty out of 102 were infected. At admission, procalcitonin (median: 3.58 ng/mL vs 0.52 ng/mL, p < 0.001) and presence of fever (25% vs 4%, p = 0.007) were different between episodes with and without proven bacterial infection in both univariate and multivariate analysis. Whole blood count, neutrophils count, neutrophils-to-lymphocytes count ratio and presence of hypothermia were not different between both groups. The diagnostic performance analysis for procalcitonin revealed an area under the curve of 0.87 with an optimal cutoff of 1.44 ng/mL leading to a sensitivity of 0.90 and a specificity of 0.76. Combining procalcitonin and presence of fever allowed to distinguish proven bacterial infection episodes from those without proven bacterial infection. Indeed, all patients with procalcitonin level of more than 1.44 ng/mL and fever had proven bacterial infection episodes. The presence of one of these 2 markers was associated with 46% of proven bacterial infection episodes. No afebrile patient with procalcitonin level less than 1.44 ng/mL had a proven bacterial infection.ConclusionAt admission, combining procalcitonin and presence of fever may be of value to distinguish ketoacidosis patients with and without proven bacterial infection, admitted in intensive care unit.

Advances in molecular diagnostic tests for pneumonia.

Pneumonia is the main global cause of sepsis, and has been associated with high morbidity and high short and long-term mortality rates. As it may be caused by a wide spectrum of microorganisms, microbial diagnosis is challenging and the choice of adequate therapy remains an important problem. This review focuses on recently published studies of microbiological diagnostic tests and clinical assessments for pneumonia, including community-acquired pneumonia, hospital-acquired pneumonia, and ventilator-associated pneumonia. Over the past decade, the microbiological diagnosis of pneumonia has improved significantly - thanks to the development and implementation of molecular diagnostic tests for identifying the most frequent pathogens causing pneumonia and for determining their patterns of resistance. Molecular methods for the diagnosis of pneumonia focus on multiple target detection systems and pathogen detection arrays, and, more recently, have been used in combination with mass spectrometry. The implementation of rapid diagnostic techniques in routine clinical practice able to identify and determine the resistance patterns of the causative microbes may transform the management of pneumonia, improving the selection and administration of antimicrobial therapies especially in critically ill patients. The validation of new diagnostic technology platforms is crucial in order to assess their usefulness and to guide antimicrobial treatment in this population.

Impact of adherence to surgical and non-surgical components of infective endocarditis guidelines and recommendations

BackgroundInfective endocarditis (IE) is associated with significant morbidity and mortality. Non-adherence to IE guidelines and recommendations is frequent, and may adversely impact patient outcomes. AimTo assess the impact of non-adherence to components of existing IE guidelines and recommendations on a composite outcome consisting of any of the following: mortality, unplanned cardiac surgery, embolic event or relapse of positive blood culture within six months of diagnosis. MethodsA single centre, retrospective cohort study. ResultsAmongst 157 patients, there was inconsistent adherence to: initial diagnosis of an infective condition (87%), timely administration of antimicrobial therapy (82%), appropriateness of predominant antimicrobial regime (94%), appropriate management of the portal of entry (86%), multidisciplinary input (75%), end of antimicrobial therapy repeat echocardiography (60%) and adherence to indications for surgery (76%). Inpatient mortality was 12.1% (n = 19) and the composite adverse outcome occurred in 36 (22.9%) patients. In multivariate logistic regression analysis, infection of prosthetic device (adjusted odds ratio [95% confidence interval]; 2.43 [1.07–5.50]) and non-adherence to surgical guidelines (aOR 3.67 [1.60–8.47]) were significantly associated with an adverse outcome. ConclusionsOur data suggests that adherence to differing components of IE management guidelines and recommendations varies and that non-adherence to surgical aspects of guidelines has the biggest impact in determining outcomes.

Peripherally inserted central venous catheter placed and maintained by a dedicated nursing team for the administration of antimicrobial therapy vs. another type of catheter: a retrospective case–control study

IntroductionData concerning the use of peripherally inserted central catheters (PICC) for the administration of intravenous (IV) antimicrobials in the acute care setting is scarce. MethodsWe performed a single-center retrospective case–control study (1:1). Case subjects were defined as patients who received IV antimicrobial treatment through a PICC line placed and maintained by specifically trained nurses (PICC group). Control subjects were defined as patients who received antimicrobial therapy by a peripheral or a central venous catheter (CVC) (control group). Control subjects were matched by type of antimicrobial, causative microorganism of the infection that was being treated and duration of treatment. An event leading to undesired catheter removal (ELUCR) was defined as any circumstance which lead to the removal of the indwelling catheter other than the completion of the scheduled course of antimicrobial therapy. ResultsThe study included 50 patients in each group. The total follow-up time was 1376 catheter-days for the PICC group and 1362 catheter-days for the control group. We observed a significantly lower incidence of ELUCR in the PICC group (0.2 versus 7.7 events per 100 catheter-days; P<0.001). When the incidence of ELUCR was analyzed according to the duration of indwelling catheterisation for each type of catheter (divided into one-week intervals), differences between both groups were also significant (P-values≤0.001 for the first three weeks of treatment). During the second week of IV treatment, only one patient in the PICC group (2.1%) developed an ELUCR compared to 19 (38.8%) in the control group (P<0.001). ConclusionsA PICC placed and maintained by a dedicated nursing team is an excellent alternative to peripheral venous catheters or CVCs for administrating antimicrobial therapy for both short and long periods of treatment.

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.

Biliary system functional condition in patients with chronic cholecystitis against the background of diabetes mellitus type 2

Overlay of diseases of the biliary system to diabetes mellitus type 2 can contribute to the enhancement of disorders of protein, lipid and carbohydrate metabolism and affect the mechanisms of regulation at the cellular molecular level. Therefore, the need for early diagnosis and study of the features of the course of chronic cholecystitis against the background of diabetes mellitus type 2 is a pressing issue of internal medicine. The motor-evacuation and cholecretory functions of the biliary system and the features of the course of chronic cholecystitis on the background of diabetes mellitus type 2 were studied. 93 patients were examined, of which 62 were patients with combined diabetes mellitus type 2 and chronic cholecystitis and 31 patients with isolated chronic cholecystitis. The control group was represented by 20 apparantly healthy individuals, who were representative of the age and number of male and female probands. The course of chronic cholecystitis was found to be accompanied by impaired gallbladder motor (evacuation) function, which was manifested by an increase in the latency period, the volume of the cavity of the gallbladder, the emptying coefficients in the dynamics and a decrease in the index of contraction of the gallbladder. In the presence of diabetes mellitus type 2, an atypical course of chronic cholecystitis may be formed, characterized by motor-evacuation disorders of the biliary tract and physico-chemical changes in bile, the severity of which exceeds those of isolated chronic cholecystitis. The peculiarities of the course of chronic cholecystitis in patients with diabetes mellitus type 2 are manifested by insignificant clinical symptoms and distinct changes at both stages of cholecystosonography, which may be the result of the development of autonomic neuropathy. In diabetes mellitus type 2, it is advisable to determine the status of the gallbladder (cholecystosonography) in order to prevent the risk of complications (cholelithiasis) and timely administration of antimicrobial therapy in the presence of an additional inflammation.

Direct antimicrobial susceptibility testing of bloodstream infection on SlipChip

This paper describes an integrated microfluidic SlipChip device for rapid antimicrobial susceptibility testing (AST) of bloodstream pathogens in positive blood cultures. Unlike conventional AST methods, which rely on an overnight subculture of positive blood cultures to obtain isolated colonies, this device enables direct extraction and enrichment of the bacteria from positive blood cultures by dielectrophoresis. SlipChip technology enables parallel inoculation of the extracted bacteria into nanoliter-scale broth droplets to perform multiplexed ASTs simultaneously. The nanoliter confinement in the droplets increases the effective inoculation amount of the bacteria, shortens the diffusion distance of nutrient elements and gases, and allows faster growth and proliferation rates. Entropy-based image analysis used for the characterization of bacterial susceptibility patterns eliminates the requirement for single-cell morphological analysis and fluorescence labeling. As a proof-of-concept, the susceptibility patterns of Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 6538p, and a positive blood culture containing Escherichia coli against several broad-spectrum antibiotics were determined by the SlipChip device. The on-chip AST results were well matched with those respectively reported by the broth microdilution method and a BD Phoenix Automated Microbiology System. Reliable AST results can be reported to clinicians within 3–8 h using this simple device after positive blood culture, allowing earlier proper administration of antimicrobial therapy.

297. Risk Factors for Infections in Open Fractures

BackgroundOpen fractures are more prone to get infected. Known risk factors are high grade Gustilo and patients’ co-morbidities, while early antibiotic administration and surgical debridement decrease the risk of infection. There is little data regarding the preferred antimicrobial therapy, timing, and duration of treatment, especially in the era of antimicrobial resistance. The aim of our study was to compare patients with and without infections after open fractures, and identify risk factors for infections, including timing of antimicrobial first dose and its duration.MethodsA historical cohort study was conducted in a secondary hospital. All adult patients admitted to the hospital with an open fracture of the limbs, between January 1, 2012 and December 31, 2016 were included in the study. Epidemiological, clinical, and microbiological data were collected and analyzed. Microbiological infection was defined by positive wound cultures during first 30 days, and clinical infection as defined by the treating physician.ResultsOne hundred sixty-seven patients were included in the study. One hundred sixty patients (95%) were treated with a first generation cephalosporine, and 55 (33%) were also treated with aminoglycosides. Microbiological infection was identified in 12 (7%) patients, and clinical infection in 27 (16%) patients. All patients received the first dose of antimicrobial therapy within 15 hours of admission (median 1.29 hours). Early administration of the first dose of antimicrobial therapy did not reduce the risk of infection (median of 1.06 hours for patients who developed infection vs. 1.31 hours for patients that did not develop infection, P = 0.58). Duration of treatment was not correlated to the risk of infection (1–3 days vs. 4–7 days, P = 0.6). In multivariate logistic regression, only location of fracture in the lower limbs was associated with an increased risk of infection (OR 4.654, CI 1.407–15.398), and Gustilo grade 1 or 2 were associated with decreased risk of infection (OR 0.301, CI 0.104–0.872).ConclusionIn our cohort, neither early administration of antimicrobial therapy, nor prolonged duration of treatment, reduced the risk of infection in open fractures.Disclosures All authors: No reported disclosures.

Lung ultrasound for diagnosis and monitoring of ventilator-associated pneumonia.

Ventilator-associated pneumonia (VAP) is the most frequent nosocomial infection in intensive care units (ICU) and is associated with increased mortality, use of antimicrobials, longer mechanical ventilation, and higher healthcare costs. Lung ultrasonography (LUS) can be used at the bedside and gained widespread acceptance in ICU. Although the visualization of a single LUS sign cannot be considered specific for a diagnosis, clinically-driven LUS examination in particular setting and clinical conditions allow ruling in or out quickly and accurately several causes of acute respiratory failure. This article reviews LUS signs for VAP diagnosis and summarizes the studies testing LUS for VAP diagnosis and monitoring. Many VAP occurs in already injured regions, thus presence of lobar consolidation is not enough to affirm VAP. However, a linear/arborescent air-bronchogram confirms the diagnosis of VAP with a good specificity, a normal LUS rules out the diagnosis of VAP (in experimented hands). LUS, thanks to its bedside ready availability, has the potential to become a key tool in early VAP diagnosis. LUS could ideally represent the decision-making tool for antimicrobial therapy administration in the timeframe of the technical time required for bronchoalveolar lavage analysis. A systematic approach for diagnosis and monitoring of VAP with LUS is also proposed in this review. But specific data on LUS specificity and sensitivity for the diagnosis of VAP are still lacking and should be investigated.

Predicting in-hospital mortality in pneumonia-associated septic shock patients using a classification and regression tree: a nested cohort study

BackgroundPneumonia complicated by septic shock is associated with significant morbidity and mortality. Classification and regression tree methodology is an intuitive method for predicting clinical outcomes using binary splits. We aimed to improve the prediction of in-hospital mortality in patients with pneumonia and septic shock using decision tree analysis.MethodsClassification and regression tree models were applied to all patients with pneumonia-associated septic shock in the international, multicenter Cooperative Antimicrobial Therapy of Septic Shock database between 1996 and 2015. The association between clinical factors (time to appropriate antimicrobial therapy, severity of illness) and in-hospital mortality was evaluated. Accuracy in predicting clinical outcomes, sensitivity, specificity, and area under receiver operating curve of the final model was evaluated in training (n = 2111) and testing datasets (n = 2111).ResultsThe study cohort contained 4222 patients, and in-hospital mortality was 51%. The mean time from onset of shock to administration of appropriate antimicrobials was significantly higher for patients who died (17.2 h) compared to those who survived (5.0 h). In the training dataset (n = 2111), a tree model using Acute Physiology and Chronic Health Evaluation II Score, lactate, age, and time to appropriate antimicrobial therapy yielded accuracy of 73% and area under the receiver operating curve 0.75. The testing dataset (n = 2111) had accuracy of 69% and area under the receiver operating curve 0.72.ConclusionsOverall mortality (51%) in patients with pneumonia complicated by septic shock is high. Increased time to administration of antimicrobial therapy, Acute Physiology and Chronic Health Evaluation II Score, serum lactate, and age were associated with increased in-hospital mortality. Classification and regression tree methodology offers a simple prognostic model with good performance in predicting in-hospital mortality.