Adequate Empirical Antibiotic Therapy Research Articles

Effect of adequacy of empirical antibiotic therapy for hospital-acquired bloodstream infections on intensive care unit patient prognosis: a causal inference approach using data from the Eurobact2 study

ObjectivesHospital-acquired bloodstream infections (HA-BSI) in the intensive care unit (ICU) are common life-threatening events. We aimed to investigate the association between early adequate antibiotic therapy and 28-day mortality in ICU patients who survived at least 1 day after the onset of HA-BSI. MethodsWe used individual data from a prospective, observational, multicentre, and intercontinental cohort study (Eurobact2). We included patients who were followed for ≥1 day and for whom time-to-appropriate treatment was available. We used an adjusted frailty Cox proportional-hazard model to assess the effect of time-to-treatment-adequacy on 28-day mortality. Infection- and patient-related variables identified as confounders by the Directed Acyclic Graph were used for adjustment. Adequate therapy within 24 hours was used for the primary analysis. Secondary analyses were performed for adequate therapy within 48 and 72 hours and for identified patient subgroups. ResultsAmong the 2418 patients included in 330 centres worldwide, 28-day mortality was 32.8% (n = 402/1226) in patients who were adequately treated within 24 hours after HA-BSI onset and 40% (n = 477/1192) in inadequately treated patients (p < 0.01). Adequacy within 24 hours was more common in young, immunosuppressed patients, and with HA-BSI due to Gram-negative pathogens. Antimicrobial adequacy was significantly associated with 28-day survival (aHR, 0.83; 95% CI, 0.72–0.96; p 0.01). The estimated population attributable fraction of 28-day mortality of inadequate therapy was 9.15% (95% CI, 1.9–16.2%). DiscussionIn patients with HA-BSI admitted to the ICU, the population attributable fraction of 28-day mortality of inadequate therapy within 24 hours was 9.15%. This estimate should be used when hypothesizing the possible benefit of any intervention aiming at reducing the time-to-appropriate antimicrobial therapy in HA-BSI.

Performance and impact of rapid multiplex PCR on diagnosis and treatment of ventilated hospital-acquired pneumonia in patients with extended-spectrum β-lactamase-producing Enterobacterales rectal carriage

BackgroundAntimicrobial stewardship (AMS) for ventilator-associated pneumonia (VAP) or ventilated hospital-acquired pneumonia (vHAP) in extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) carriers is challenging. BioFire® FilmArray® Pneumonia plus Panel (mPCR) can detect bacteria and antibiotic resistance genes, including blaCTX-M, the most common ESBL-encoding gene.MethodsThis monocentric, prospective study was conducted on a group of ESBL-E carriers from March 2020 to August 2022. The primary objective was to evaluate the concordance between the results of mPCR and conventional culture performed on respiratory samples of ESBL-E carriers to investigate suspected VAP/vHAP. The secondary objective was to appraise the impact of performing or not mPCR on initial antibiotic therapy adequacy in ESBL-E carriers with confirmed VAP/vHAP.ResultsOver the study period, 294 patients with ESBL-E carriage were admitted to the ICU, of who 168 (57%) were mechanically ventilated. (i) Diagnostic performance of mPCR was evaluated in suspected 41 episodes of VAP/vHAP: blaCTX-M gene was detected in 15/41 (37%) episodes, where 9/15 (60%) were confirmed ESBL-E-induced pneumonia. The culture and blaCTX-M were concordant in 35/41 (85%) episodes, and in all episodes where blaCTX-M was negative (n = 26), the culture never detected ESBL-E. (ii) The impact of mPCR on initial antibiotic therapy adequacy was assessed in 95 episodes of confirmed VAP/vHAP (22 episodes were tested with mPCR and 73 without); 47 (49%) episodes were ESBL-E-induced, and 24 (25%) were carbapenem-resistant bacteria-induced. The use of mPCR was significantly associated with higher prescription of adequate empirical antibiotic therapy in the multivariable logistic regression (adjusted odds ratio (aOR) (95% CI) of 7.5 (2.1–35.9), p = 0.004), propensity-weighting (aOR of 5.9 (1.6–22.1), p = 0.008), and matching-cohort models (aOR of 5.8 (1.5–22.1), p = 0.01).ConclusionmPCR blaCTX-M showed an excellent diagnostic value to rule out the diagnosis of ESBL-E related pneumonia in ESBL-E carriers with suspected VAP/vHAP. In addition, in patients with confirmed VAP/vHAP, a mPCR-based antibiotic therapy was associated with an increased prescription of adequate empirical antibiotic therapy. Performing mPCR on respiratory samples seems to be a promising tool in ESBL-E carriers with suspected vHAP/VAP. However, if mPCR is used in very low pre-test clinical probability of pneumonia, due to the high sensitivity and the rate of overdiagnosed pneumonia, the risk of overconsumption of carbapenem may prevail. Further studies are warranted.

Local Antimicrobial Resistance Trends in Pediatric Urinary Tract Infection: The Importance of Local Surveillance of a Global Problem.

Introduction Urinary tract infections (UTIs) are one of the most common pediatric bacterial infections and consequently a major reason for antibiotic treatment. Despite being a global problem, antimicrobial resistance is often geographically heterogeneous. Thus, it is fundamental to know local epidemiology and practice frequent surveillance of each hospital's antibiograms. The aims of this study areto determine the local antimicrobial resistance profile in pediatric UTIs, to understand its evolution over 14 years, and finally, to infer if the currently instituted antibiotic empirical therapy remains effective. Materials and methods A retrospective observational study was performed through the analysis of urine cultures and respective antibiograms of children diagnosed with UTIfrom 2017 to 2019 in Centro Hospitalar Universitário do Algarve (Faro's unit, Portugal), followed by a comparison of the obtained datawith the results of a similar study performed between 2003 and 2005. Results A total of 784 urine cultures were selected. Escherichia coli was the most frequent microorganism (n = 561; 71.56%), followed by Proteus mirabilis (n = 117; 14.92%) and Klebsiella pneumoniae (n = 40; 5.10%). The most commonly prescribed antibiotic was cefuroxime axetil (66.28%). Escherichia coli had an increase in resistance to amoxicillin-clavulanate of 6.16% to 34.76% and cefuroxime axetil of 0.73% to 4.46%. Proteus mirabilis had an increase in resistance to amoxicillin-clavulanate of 1.64% to 11.11%. Klebsiella pneumoniae had an increase in resistance to cefuroxime axetil (0%-27.50%) and nitrofurantoin (0%-47.50%). The three microorganisms showed a decrease in trimethoprim-sulfamethoxazole resistance profiles, as well as low resistance profiles to fosfomycin. In fifty cases in which antibiotic empirical therapy was instituted, the isolated microorganism revealed in vitro resistance; 37 of these cases had a good evolution, maintaining the antibiotic empirical therapy. Discussion Local surveillance of antimicrobial resistanceallows monitoring of the resistance trends and adequacy of empirical antibiotic therapy. This study's local resistance profile was distinct from other regions of the country and the world. Continuous local surveillance also potentiates the dissemination of the results to the concerned healthcare providers and the initiation of timely responsive measures, containing the increase in antimicrobial resistance. As Escherichia coli was the commonest isolated microorganism, its antimicrobial profile should dictate antibiotic empirical therapy. This study supports that in vitro is not equivalent to in vivo resistance. Conclusion There was a significant increase in antimicrobial resistance profiles, especially to amoxicillin-clavulanate. Cefuroxime axetil remains the recommended antibiotic for empirical therapy in this hospital, although fosfomycin should be considered as an alternative in non-complicated cystitis in adolescent females. This study reinforces the importance of continuous local resistance surveillance as a preventive measure against the global increase in antimicrobial resistance.

Microbiological profile of patients treated for postoperative peritonitis: temporal trends 1999–2019

BackgroundTemporal changes in the microbiological resistance profile have been reported in several life-threatening infections. However, no data have ever assessed this issue in postoperative peritonitis (POP). Our purpose was to assess the rate of multidrug-resistant organisms (MDROs) in POP over a two-decade period and to analyse their influence on the adequacy of empirical antibiotic therapy (EAT).MethodsThis retrospective monocentric analysis (1999–2019) addressed the changes over time in microbiologic data, including the emergence of MDROs and the adequacy of EAT for all intensive care unit adult patients treated for POP. The in vitro activities of 10 antibiotics were assessed to determine the most adequate EAT in the largest number of cases among 17 antibiotic regimens in patients with/without MDRO isolates. Our primary endpoint was to determine the frequency of MDRO and their temporal changes. Our second endpoint assessed the impact of MDROs on the adequacy of EAT per patient and their temporal changes based on susceptibility testing. In this analysis, the subgroup of patients with MDRO was compared with the subgroup of patients free of MDRO.ResultsA total of 1,318 microorganisms were cultured from 422 patients, including 188 (45%) patients harbouring MDROs. The growing proportions of MDR Enterobacterales were observed over time (p = 0.016), including ESBL-producing strains (p = 0.0013), mainly related to Klebsiella spp (p < 0.001). Adequacy of EAT was achieved in 305 (73%) patients. Decreased adequacy rates were observed when MDROs were cultured [p = 0.0001 vs. MDRO-free patients]. Over the study period, decreased adequacy rates were reported for patients receiving piperacillin/tazobactam in monotherapy or combined with vancomycin and imipenem/cilastatin combined with vancomycin (p < 0.01 in the three cases). In patients with MDROs, the combination of imipenem/cilastatin + vancomycin + amikacin or ciprofloxacin reached the highest adequacy rates (95% and 91%, respectively) and remained unchanged over time.ConclusionsWe observed high proportions of MDRO in patients treated for POP associated with increasing proportions of MDR Enterobacterales over time. High adequacy rates were only achieved in antibiotic combinations involving carbapenems and vancomycin, while piperacillin/tazobactam is no longer a drug of choice for EAT in POP in infections involving MDRO.Graphical

Machine learning model for the prediction of gram-positive and gram-negative bacterial bloodstream infection based on routine laboratory parameters

BackgroundBacterial bloodstream infection is responsible for the majority of cases of sepsis and septic shock. Early recognition of the causative pathogen is pivotal for administration of adequate empiric antibiotic therapy and for the survival of the patients. In this study, we developed a feasible machine learning (ML) model to predict gram-positive and gram-negative bacteremia based on routine laboratory parameters.MethodsData for 2118 patients with bacteremia were obtained from the Medical Information Mart for Intensive Care dataset. Patients were randomly split into the training set and test set by stratified sampling, and 374 routine laboratory blood test variables were retrieved. Variables with missing values in more than 40% of the patients were excluded. Pearson correlation test was employed to eliminate redundant features. Five ML algorithms were used to build the model based on the selected features. Additionally, 132 patients with bacteremia who were treated at Qilu Hospital of Shandong University were included in an independent test cohort to evaluate the model.ResultsAfter feature selection, 32 variables remained. All the five ML algorithms performed well in terms of discriminating between gram-positive and gram-negative bacteremia, but the performance of convolutional neural network (CNN) and random forest (RF) were better than other three algorithms. Consider of the interpretability of models, RF was chosen for further test (ROC-AUC = 0.768; 95%CI = 0.715–0.798, with a sensitivity of 75.20% and a specificity of 63.79%). To expand the application of the model, a decision tree (DT) was built utilizing the major variables, and it achieved an AUC of 0.679 (95%CI = 0.632–0.723), a sensitivity of 66%, and a specificity of 67.82% in the test cohort. When tested in the Qilu Hospital cohort, the ROC-AUC of the RF and DT models were 0.666 (95%CI = 0.579–0.746) and 0.615 (95%CI = 0.526–0.698), respectively. Finally, a software was developed to make the RF- and DT-based prediction models easily accessible.ConclusionThe present ML-based models could effectively discriminate between gram-positive and gram-negative bacteremia based on routine laboratory blood test results. This simple model would be beneficial in terms of guiding timely antibiotic selection and administration in critically ill patients with bacteremia before their pathogen test results are available.

Impact of empiric antibiotic therapy on the clinical outcome of acute calculous cholecystitis

PurposeAlthough mortality and morbidity of severe acute calculous cholecystitis (ACC) are still a matter of concern, the impact of inadequate empirical antibiotic therapy has been poorly studied as a risk factor. The objective was to assess the impact of the adequacy of empirical antibiotic therapy on complication and mortality rates in ACC.MethodsThis observational retrospective cohort chart-based single-center study was conducted between 2012 and 2016. A total of 963 consecutive patients were included, and pure ACC was selected. General, clinical, postoperative, and microbiological variables were collected, and risk factors and consequences of inadequate treatment were analyzed.ResultsBile, blood, and/or exudate cultures were obtained in 76.3% of patients, more often in old, male, and severely ill patients (P < 0.001). Patients who were cultured had a higher overall rate of postoperative complications (47.4% vs. 29.7%; P < 0.001), as well as of severe complications (11.6% vs. 4.7%; P = 0.008). Patients with positive cultures had more overall complications (54.8% vs. 39.6%; P = 0.001), more severe complications (16.3% vs. 6.7%; P = 0.001), and higher mortality rates (6% vs. 1.9%; P = 0.012). Patients who received inadequate empirical antibiotic therapy had a fourfold higher mortality rate than those receiving adequate therapy (n = 283; 12.8% vs. 3.4%; P = 0.003). This association was especially marked in severe ACC TG–III patients (n = 132; 18.2 vs. 5.1%; P = 0.018) and remained a predictor of mortality in a binary logistic regression (OR 4.4; 95% CI 1.3–15.3).ConclusionPatients with positive cultures developed more complications and faced higher mortality. Adequate empirical antibiotic therapy appears to be of paramount importance in ACC, particularly in severely ill patients.

Intractable complicated course of tricuspid valve infective endocarditis due to non-compliance of treatment with clinical guidelines with a decisive role of molecular biological study in etiological diagnosis: a case report

A clinical observation of the treatment non-compliance consequences with clinical guidelines and principles of empirical therapy selection in a female patient with intravenous drug abuse, viral hepatitis C and HIV infection, with a history of a COVID-19 and the development of uncontrolled staphylococcal infective endocarditis (IE) of the tricuspid valve, complicated recurrence of early prosthetic IE is presented. Successful treatment was achieved only by a combination of tricuspid valve replacement and the appointment of etiotropic therapy for S. aureus (MSSA). The typical clinical scenario was not accompanied by the choice of adequate empirical antibiotic therapy, despite the high suspicion of association with MSSA, which determined the complicated course of IE. Only the polymerase chain reaction of the heart valve tissue played a key role in the etiological diagnosis. The use of valve tissue polymerase chain reaction in addition to traditional microbiological methods is a valuable diagnostic study.

Epidemiology and outcome of anaerobic bacteremia in a tertiary hospital

Despite a low incidence, anaerobic bacteremia remains a serious and often underestimated condition. This retrospective study aims to describe the epidemiology of anaerobic bacteremia and to identify risk factors affecting mortality and the impact of treatment. We included all positive anaerobic blood cultures from January 2018 to December 2019 at the University Hospital of Charleroi (Belgium). We identified 105 episodes of clinically significant anaerobic bacteremia (mean age of patients: 66.4 +/- 16.8 years). The main comorbidities were hypertension, chronic kidney disease, and diabetes. Bacteremia was community-acquired in 70.5% of the episodes. Two thirds of the blood cultures were mono-microbial, and the commonest bacteria found were Bacteroides fragilis group (31.4%), Fusobacterium spp. (17.1%) and Clostridium spp. (15.2%). The main sources of bacteremia were abdominal (35.2%), urinary (17.1%), osteoarticular (14.2%) and pulmonary (12.3%). Surgery within 30 days before hospitalization was more frequent in patients with nosocomial bacteremia (45.2% vs 2.7%, p < 0.0001). An appropriate empirical antibiotic therapy was initiated in 74.7% of patients, and the median duration of antibiotic therapy was 10 [5 - 15] days. One third of patients had a surgical management. Patients who did not survive at day 30 (n = 23 [21.9%]) had significantly lower time to positivity (TTP) values than patients alive at day 30, presented more often with sepsis, had higher Charlson scores and chronic kidney disease, and were more likely to suffer from Clostridium spp. bacteremia. In a Cox proportional hazard analysis, sepsis (OR: 7.32 [95% CI: 2.83– 18.97], p< 0.0001) was identified as an independent risk factors for 30-day mortality, whereas time to positivity ≥ 30 h (OR: 0.24 [95% CI: 0.07 – 0.84], p = 0.025) and an adequate empirical antibiotic therapy (OR: 0.37 [95% CI: 0.15 – 0.94], p = 0.037) were associated with better outcomes. Anaerobic bacteremia has a high mortality rate which justifies the maintenance of empirical antibiotic therapy.

Paediatric and adult patients from New Caledonia Island admitted to the ICU for community-acquired Panton-Valentine leucocidin-producing Staphylococcus aureus infections

Severe infections involving Panton-Valentine leukocidin-producing Staphylococcus aureus (PVL + Sa) are increasing. This monocentre, retrospective descriptive cohort assessed clinical characteristics and outcome of paediatric and adult patients admitted for community-acquired PVL + Sa infections to the unique intensive care unit (ICU) on New Caledonia Island. Overall, 72 patients (including 23 children) admitted for acute respiratory failure (42%), sepsis/septic shock (21%), and/or postoperative care (32%) were analysed. Most patients had pulmonary (64%), skin/soft tissue (SSTI) (54%) and/or osteoarticular (38%) infections. Multifocal infections (≥ 2 sites) and bacteraemia were reported in 65% and 76% of the patients, respectively. Methicillin-resistant S. aureus isolates were reported in 61% of adult cases versus 30% in children (p < 0.05). Mechanical ventilation, vasoactive support and source control were administered in 53%, 43% and 58% of the patients, respectively. All paediatric patients received adequate empirical antibiotic therapy versus 30/49 adults (p < 0.001). Adequate documented therapy was obtained ≤ 72 h in 70/72 (97%) patients. Death was only reported in adults (n = 10 (14%)), mainly during pulmonary infection (22%), SSTIs (21%) and bacteraemia (24%)). In summary, in ICU patients from New Caledonia Island the clinical presentation of severe community-acquired PVL + Sa infections seems different from Western European observations with high rates of multifocal infections and methicillin-resistant strains.

Current application of antibiotic de-escalation treatment in children with sepsis and its impact on prognosis

Objective: To analyze the eligibility of empirical antibiotic therapy in culture positive sepsis in the pediatric intensive care unit (PICU), and to explore the application of antibiotic de-escalation (ADE) in children with sepsis and its impact on prognosis. Methods: A total of 123 children with sepsis-associated organ dysfunction or septic shock admitted to the PICU of Shengjing Hospital of China Medical University from January 2018 to December 2020 were retrospectively analyzed. The general information, laboratory tests, the use of empirical anti-bacterial drugs and the application of ADE were collected. According to the adjustment of anti-bacterial drugs, these children were divided into ADE group and non-ADE group. Comparisons between groups were performed with unpaired Student t test, or Mann-Whitney U test, or chi-square test or Fisher exact test. Results: In these 123 children, 70 were males and 53 were females, the age was 11.4 (2.8, 56.5) months. Body fluid culture was detected positive in 41 children including 3 children (7.3%) who received inadequate empirical antibiotic therapy and 38 children (92.7%) who received adequate empirical antibiotic therapy. Excluding 10 children who received appropriate therapy, 28 received unnecessary broad-spectrum antibiotics. There were no significant differences regarding the PICU all-cause mortality rates, length of PICU stay, hospitalization cost, duration of mechanical ventilation, as well as incidences of re-infection between the ADE group (n=46) and non-ADE group (n=77) (all P>0.05). However, among the 101 children who have used antibiotics against multidrug-resistant organism, the duration of such antibiotics use in ADE group (n=43) was shorter than that in non-ADE group (n=58) (5.0 (4.0, 12.0) vs. 9.5 (7.0, 13.0) d, Z=-3.14, P=0.002). Conclusions: Overuse of unnecessary broad-spectrum empirical antibiotics is very common, but the application of ADE is rather disappointing. ADE can reduce the use of anti-bacterial drugs against multi-drug resistant bacteria without significant adverse effects on prognosis in children with sepsis.

Protocolo terapéutico empírico de la sepsis

A group of measures has demonstrated to be very effective in reducing the high mortality of sepsis. First-line actions involve a practically immediate approach to a septic patient and include monitoring, evaluation of the source, extraction of blood cultures, adequate empirical antibiotic therapy in the first hour, and infusion of at least 30ml/kg of intravenous crystalloid fluids within the first three hours at the same time that determination of lactate, procalcitonin, and other analytical parameters is performed in order to quantifying organ damage. After the initial approach are second-line actions, in which control of the source of the infection must be proposed if necessary, reevaluating the presence of septic shock (need for vasopressors and lactate clearance), and considering the suitability of certain techniques (renal replacement therapy or ventilatory support) which in turn will determine ICU admission.

Clinical characteristics and risk factors for mortality in children with Pseudomonas aeruginosa bacteraemia: A retrospective review at a paediatric tertiary centre.

The objective of this study was to describe clinical features and to assess the risk factors associated with mortality in Pseudomonas aeruginosa bacteraemia in a tertiary Japanese paediatric care hospital. Patients diagnosed with P. aeruginosa bacteraemia at our hospital between 2007 and 2018 were analysed in a retrospective case series. Inadequate initial therapy for P. aeruginosa bacteraemia was defined as initial treatment without antipseudomonal antibiotics or an administration of antipseudomonal agent to which the causative strain was resistant. Bacteraemia-related death was defined as all deaths occurring within 7 days after the onset of bacteraemia. Overall, 41 patients with 42 P. aeruginosa bacteraemia episodes were identified. The most common underlying condition was malignancy (27%), followed by congenital heart disease (20%) and preterm birth (17%). Among the 42 P. aeruginosa clinical isolates, 24% were resistant to at least one of the antipseudomonal agents and 10% were resistant to more than one agent. The susceptibility levels for piperacillin, fourth-generation cephalosporins and ciprofloxacin were higher than that for carbapenems. Bacteraemia-related death was observed in 43% of episodes. The 30-day all-cause mortality was 50% (standard error 8%). Neonates, intensive care, mechanical ventilation, afebrile episodes, septic shock, hypoxia, renal injury and inadequate initial therapy were associated with bacteraemia-related death episodes. We found that childhood P. aeruginosa bacteraemia is still a high mortality disease. Our results imply the importance of the identification of high-risk patients and the establishment of adequate empirical antibiotic therapy.

EFFECT OF EMPIRICAL ANTIBIOTIC THERAPY ON THE CLINICAL OUTCOME OF ACUTE CALCULOUS CHOLECYSTITIS

Abstract INTRODUCTION Acute calculous cholecystitis (ACC) is the second surgical cause of emergency consultation in the Western world. According to the Tokyo International Guidelines 2018 (TIG18), the treatment of choice is laparoscopic cholecystectomy in patients with mild or moderate cholecystitis. However, in severe cases there is a great variability of therapeutic options. We analyzed the adequacy of antibiotic therapy by studying intraoperative cultures (bile and peritoneal fluid) and preoperative blood cultures, to identify the effect of this antibiotic therapy on complication and mortality rates. MATERIAL AND METHODS A retrospective unicentric study on a prospective database of 725 ACCs between 2012 and 2016. More than 200 general, clinical, postoperative and microbiological variables are collected, including the antibiogram of the isolated germs in order to determine the adequacy of each administered antibiotic. RESULTS Cultures were performed in 76.1% of the cases, with a greater tendency to cultivate in older patients, men or with greater severity according to TIG18 (p &amp;lt; 0.001). Cultured patients had a higher rate of postoperative complications (p = 0.001). Patients who received adequate empirical antibiotic therapy had a lower rate of complications (50% vs 64%;p=0.037) and lower mortality (2.8% vs 11.8%;p=0.003) compared to patients with resistant germs to the antibiotic therapy given, especially important in severe ACC (3.7% vs 15.7%;p=0.022). CONCLUSIONS Adequate empirical antibiotic therapy is associated with fewer complications, as well as a lower mortality rate, especially in severe ACCs. Patients with severe ACC will probably require empirical broad-spectrum antibiotic coverage.

Understanding and Managing Sepsis in Patients With Cancer in the Era of Antimicrobial Resistance.

Sepsis is a frequent complication in immunosuppressed cancer patients and hematopoietic stem cell transplant recipients that is associated with high morbidity and mortality rates. The worldwide emergence of antimicrobial resistance is of special concern in this population because any delay in starting adequate empirical antibiotic therapy can lead to poor outcomes. In this review, we aim to address: (1) the mechanisms involved in the development of sepsis and septic shock in these patients; (2) the risk factors associated with a worse prognosis; (3) the impact of adequate initial empirical antibiotic therapy given the current era of widespread antimicrobial resistance; and (4) the optimal management of sepsis, including adequate and early source control of infection, optimized antibiotic use based on the pharmacokinetic and pharmacodynamics changes in these patients, and the role of the new available antibiotics.

Effectiveness of Electronic Guidelines (GERH®) to Improve the Clinical Use of Antibiotics in An Intensive Care Unit

The objective of the study was to evaluate the capacity of GERH®-derived local resistance maps (LRMs) to predict antibiotic susceptibility profiles and recommend the appropriate empirical treatment for ICU patients with nosocomial infection. Data gathered between 2007 and 2016 were retrospectively studied to compare susceptibility information from antibiograms of microorganisms isolated in blood cultures, lower respiratory tract samples, and urine samples from all ICU patients meeting clinical criteria for infection with the susceptibility mapped by LRMs for these bacterial species. Susceptibility described by LRMs was concordant with in vitro study results in 73.9% of cases. The LRM-predicted outcome agreed with the antibiogram result in >90% of cases infected with the bacteria for which GERH® offers data on susceptibility to daptomycin, vancomycin, teicoplanin, linezolid, and rifampicin. Full adherence to LRM recommendations would have improved the percentage adequacy of empirical prescriptions by 2.2% for lower respiratory tract infections (p = 0.018), 3.1% for bacteremia (p = 0.07), and 5.3% for urinary tract infections (p = 0.142). LRMs may moderately improve the adequacy of empirical antibiotic therapy, especially for lower respiratory tract infections. LRMs recommend appropriate prescriptions in approximately 50% of cases but are less useful in patients with bacteremia or urinary tract infection.

Guideline-based treatment of urinary tract infections

Urinary tract infections (UTIs) are among the most common infections. Especially complicated UTIs have abroad bacterial spectrum, sometimes having high antibiotic resistance rates. The clinical course might be very different and can range from spontaneous cure to fulminant sepsis. Which initial therapy is adequate for which UTI entity and what are the corresponding guidelines recommendations? This is areview of the current S3 guideline urinary tract infection, the guideline parenteral initial therapy of bacterial infections from the Paul Ehrlich Society, the guideline urological infections from the European Association of Urology (EAU) and the guideline on recurrent uncomplicated UTI in women from the American Urological Association (AUA). Adequate antibiotic therapy is based on the stratification into complicated and uncomplicated, as well as upper and lower infections, and on specific risk factors (e.g., urinary tract catheter) that can be classified according to the ORENUC criteria. Based on this classification, the choice for an empirical antibiotic therapy is made. The spectrum of pathogens should therefore be limited in order to use antibiotics with anarrow spectrum of activity and little collateral damage if possible, thus, preventing both the development of resistance and complications. Adequate empirical antibiotic therapy and prophylaxis in line with guidelines is based on the clinical classification and risk factors.

Searching and Finding the Hidden Treasure: A Retrospective Analysis of Rickettsial Disease Among Dutch International Travelers.

BackgroundRickettsial disease (RD) is a prevalent and underestimated cause of febrile illness worldwide, especially in the absence of an inoculation eschar. We attempted to quantify this underestimation at our clinic, by investigating past cases of febrile illness in travelers who had tested negative for leptospirosis, a disease that can initially present similarly to non-eschar RD, and which we routinely consider when other important causes of unspecified febrile illness have tested negative.MethodsWe performed a retrospective analysis in febrile returned travelers from Asia, Africa, or the Americas between 2010 and 2017, who had tested negative for leptospirosis. Serologic immunofluorescence assays were performed for Orientia tsutsugamushi (scrub typhus), typhus group, and spotted fever group RD. We performed a medical records review of all patients who tested positive. In case of a fitting medical history, cases were deemed either confirmed (based on convalescent serology) or suspected (based on single serology).ResultsAmong 97 patients, convalescent serology was available in 16 (16.5%) patients, and a single serology in 81 (83.5%) patients. RD was the likely diagnosis in 8 of 16 (50.0%) patients with convalescent serology, and in 8 of 81 (9.9%) with single serology. Of the 16 confirmed/suspected cases, 11 (69%) had been missed and 7 (44%) had not received adequate empiric antibiotic therapy.ConclusionsThis study shows that non-eschar RD is an important and poorly recognized cause of illness in travelers, even in a specialized travel clinic. A lower threshold to test and treat for RD is warranted in returning travelers with febrile illness.

Shock and Early Death in Hematologic Patients with Febrile Neutropenia.

Empirical antibiotic therapy with a beta-lactam is the standard of care in febrile neutropenia (FN) and is given to prevent early death. The addition of vancomycin is recommended in certain circumstances, but the quality of evidence is low, reflecting the lack of clinical data. In order to characterize the epidemiology of early death and shock in FN, we reviewed all episodes of FN from 2003 to 2017 at University Hospital, Federal University of Rio de Janeiro, and looked at factors associated with shock at first fever and early death (within 3 days from first fever) by univariate and multivariate analyses. Among 1,305 episodes of FN, shock occurred in 42 episodes (3.2%) and early death in 15 (1.1%). Predictors of shock were bacteremia due to Escherichia coli (odds ratio [OR], 8.47; 95% confidence interval [95% CI], 4.08 to 17.55; P < 0.001), Enterobacter sp. (OR, 7.53; 95% CI, 1.60 to 35.33; P = 0.01), and Acinetobacter sp. (OR, 6.95; 95% CI, 1.49 to 32.36; P = 0.01). Factors associated with early death were non-Hodgkin's lymphoma (OR, 3.57; 95% CI, 1.18 to 10.73; P = 0.02), pneumonia (OR, 21.36; 95% CI, 5.72 to 79.72; P < 0.001), shock (OR, 11.64: 95% CI, 2.77 to 48.86; P = 0.01), and bacteremia due to Klebsiella pneumoniae (OR, 5.91; 95% CI, 1.11 to 31.47; P = 0.03). Adequate empirical antibiotic therapy was protective (OR, 0.23; 95% CI, 0.07 to 0.81; P = 0.02). Shock or early death was not associated with Gram-positive bacteremia; catheter-related, skin, or soft tissue infection; or inadequate Gram-positive coverage. These data challenge guideline recommendations for the empirical use of vancomycin at first fever in neutropenic patients.

Community-onset Pseudomonas aeruginosa urinary sepsis in elderly people: Predictive factors, adequacy of empirical therapy and outcomes.

Purpose To know the predictive factors for Pseudomonas aeruginosa (PA) urinary sepsis in hospitalised elderly patients coming from community, the adequacy of empirical antibiotic therapy and its outcomes. Methods Retrospective case-control study conducted between 2007 and 2017. Patients aged 65years or older with PA urinary sepsis were included as cases. Three age-matched controls, with urinary sepsis caused by other microorganisms, were selected for each case. Predictors for PA urinary sepsis were determined by logistic regression analysis. Adequacy of empirical antibiotic therapy and outcomes were compared between both groups. Results A total of 332 patients, from which 83 were cases, were included. Predictive factors for PA urinary sepsis were as follows: male sex (OR 3.16, 95% CI 1.61-6.10; P<.001), urinary catheter (OR 3.25, 95% CI 1.73-6.11; P<.001) and healthcare-associated infection (OR 5.52, 95% CI 1.76 -17.29; P=.003). Inadequate empirical antimicrobial therapy (IEAT) and length of hospital stay were higher in PA group (42% vs 24%, P=.002; 7.45±4.36days vs 6.43±3.82days, P=.045, respectively), but mortality was not different (7.2% vs 8.8%, P=.648). Conclusions Pseudomonas aeruginosa urinary sepsis in elderly people was associated with male sex, urinary catheter and healthcare-associated infection. These infections had a higher rate of IEAT and a longer hospital stay than urinary sepsis caused by other microorganisms.

Optimization of starting empirical antibacterial therapy in patients with HIV infection – specialized hospital patients

Objective: to analyze the adequacy of the scheme of empirical antibiotic therapy in patients with complicated forms of HIV infection in a specialized hospital and propose a set of measures for its optimization.Materials and methods: Clinical and demographic characteristics, results of bacteriological studies, risk factors of infection with resistant and multiresistant pathogens were studied in patients with HIV infection at the stage of progression with infectious complications of bacterial etiology, and the adequacy of empirical antibiotic therapy was evaluated.Results:The analysis of bacterial infectious complications in 21 HIV-infected patients with advanced stages of the disease was carried out. It was established that the profiles of the starting ABT only in 47% of cases coincide with the results of the antibiogram. To increase the effectiveness of empirical antibacterial therapy, stratification of risk groups for the detection of multiresistant bacterial pathogens has been developed. The basis of stratification: the severity of immunodeficiency, the presence of previously conducted antibacterial therapy, the period and place of detection of infectious complications, the localization of the infectious process.Conclusion: the use in clinical practice of a differentiated approach to the appointment of antibacterial drugs for starting empirical therapy in patients with HIV infection can improve the quality of treatment of infectious complications in patients with immunosuppression.