Inadequate Empirical Treatment Research Articles

The real-world impact of the BioFire FilmArray blood culture identification 2 panel on antimicrobial stewardship among patients with bloodstream infections in intensive care units with a high burden of drug-resistant pathogens

BackgroundThe increasing prevalence of drug-resistant pathogens leads to delays in adequate antimicrobial treatment in intensive care units (ICU). The real-world influence of the BioFire FilmArray Blood Culture Identification 2 (BCID2) panel on pathogen identification, diagnostic concordance with conventional culture methods, and antimicrobial stewardship in the ICU remains unexplored. MethodsThis retrospective observational study, conducted from July 2021 to August 2023, involved adult ICU patients with positive blood cultures who underwent BCID2 testing. The concordance between BCID2 and conventional culture results was examined, and its impact on antimicrobial stewardship was assessed through a comprehensive retrospective review of patient records by intensivists. ResultsA total of 129 blood specimens from 113 patients were analysed. Among these patients, a high proportion of drug-resistant strains were noted, including carbapenem-resistant Klebsiella pneumoniae (CRKP) (57.1%), carbapenem-resistant Acinetobacter calcoaceticus-baumannii complex (100%), methicillin-resistant Staphylococcus aureus (MRSA) (70%), and vancomycin-resistant Enterococcus faecium (VRE) (100%). The time from blood culture collection to obtaining BCID2 results was significantly shorter than conventional culture (46.2 h vs. 86.9 h, p < 0.001). BCID2 demonstrated 100% concordance in genotype–phenotype correlation in antimicrobial resistance (AMR) for CRKP, carbapenem-resistant Escherichia coli, MRSA, and VRE. A total of 40.5% of patients received inadequate empirical antimicrobial treatment. The antimicrobial regimen was adjusted or confirmed in 55.4% of patients following the BCID2 results. ConclusionsIn the context of a high burden of drug-resistant pathogens, BCID2 demonstrated rapid pathogen and AMR detection, with a noticeable impact on antimicrobial stewardship in BSI in the ICU.

Impact of inadequate empirical antibiotic treatment on outcome of non-critically ill children with bacterial infections

BackgroundThe impact of inadequate empirical antibiotic treatment on patient outcomes and hospitalization duration for non-life-threatening infections in children remains poorly understood. We aimed to assess the effects of inadequate empirical antibiotic treatment on these factors in pediatric patients.MethodsThe medical records of children admitted for infectious diseases with bacteria isolated from sterile sites between 2018 and 2020 were retrospectively reviewed. Patients who received adequate empirical treatment were compared with those who received inadequate treatment in terms of demographic, clinical, and laboratory variables.ResultsForty-eight patients who received inadequate empirical antimicrobial treatment were compared to 143 patients who received adequate empirical treatment. Inadequate empirical antimicrobial treatment did not significantly affect the length of hospital stay or the incidence of complications in non-critically ill children with bacterial infections. Younger age and underlying renal abnormalities were identified as risk factors for inadequate antimicrobial treatment, while associated bacteremia was more common in the adequate antimicrobial treatment group.Conclusionsinadequate antibiotic treatment did not affect the outcomes of non-critically ill children with bacterial infectious diseases. Therefore, routine empirical broad-spectrum treatment may not be necessary for these cases, as it can lead to additional costs and contribute to antibiotic resistance. Larger prospective studies are needed to confirm these findings.

Significant increase of CTX-M-15-ST131 and emergence of CTX-M-27-ST131 Escherichia coli high-risk clones causing healthcare-associated bacteraemia of urinary origin in Spain (ITUBRAS-2 project).

To assess the microbiological characteristics of Escherichia coli causing healthcare-associated bacteraemia of urinary origin (HCA-BUO) in Spain (ITUBRAS-2 project), with particular focus on ESBL producers and isolates belonging to ST131 high-risk clone (HiRC). Clinical characteristics and outcomes associated with ST131 infection were investigated. A total of 222 E. coli blood isolates were prospectively collected from patients with HCA-BUO from 12 tertiary-care hospitals in Spain (2017-19). Antimicrobial susceptibility and ESBL/carbapenemase production were determined. ST131 subtyping was performed. A subset of 115 isolates were selected for WGS to determine population structure, resistome and virulome. Clinical charts were reviewed. ESBL-producing E. coli prevalence was 30.6% (68/222). ST131 represented 29.7% (66/222) of E. coli isolates and accounted for the majority of ESBL producers (46/68, 67.6%). The C2/H30-Rx subclone accounted for most ST131 isolates (44/66) and was associated with CTX-M-15 (37/44) and OXA-1 enzymes (27/44). Cluster C1-M27 was identified in 4/10 isolates belonging to subclade C1/H30-R1 and associated with CTX-M-27. Additionally, ST131 isolates showed a high content of other acquired resistance genes, and clade C/ST131 isolates carried characteristic QRDR mutations. They were categorized as uropathogenic E. coli and had higher aggregate virulence scores. ST131 infection was associated with more complex patients, prior use of cephalosporins and inadequate empirical treatment but was not associated with worse clinical outcomes. ST131 HiRC is the main driver of ESBL-producing E. coli causing HCA-BUO in Spain, mainly associated with the expansion of subclade CTX-M-15-C2/H30-Rx and the emergence of CTX-M-27-C1/H30-R1 (Cluster C1-M27).

Increasing Gram-Negative Catheter-Related Bloodstream Infection in Cancer Patients.

Background: We aimed to assess the incidence, etiology and outcomes of catheter-related bloodstream infection (CRBSI) in onco-hematological patients, to assess the differences between patients with hematological malignancies (HMs) and solid tumors (STs) and to identify the risk factors for Gram-negative (GN) CRBSI. Methods: All consecutive episodes of BSI in adult cancer patients were prospectively collected (2006-2020). The etiology of CRBSI was analyzed in three different 5-year periods. Risk factors for GN CRBSI were assessed in the whole cohort and separately in patients with HMs and STs. Results: Among 467 episodes of monomicrobial CRBSI, 407 were Gram-positive (GP) (87.1%), 49 GN (10.5%) and 11 fungal (2.4%). Hematological patients (369 episodes) were more frequently neutropenic and were more likely to carry central venous catheters and develop GP CRBSI. Patients with STs (98 episodes) had more comorbidities, more frequently carried port reservoirs and commonly presented more GN CRBSI. GN CRBSI significantly increased over the study period, from 5.2% to 23% (p < 0.001), whereas GP CRBSI decreased from 93.4% to 73.3% (p < 0.001). CRBSI episodes involving port reservoirs and peripherally-inserted central catheters were significantly increased (p < 0.001). The most frequent GPs were coagulase-negative staphylococci (CoNS) (57.8%) and Pseudomonas aeruginosa was the most common GN (3%). Multidrug-resistant (MDR) GN represented 32.7% of all GN CRBSIs and increased over time (p = 0.008). The independent risk factors for GN CRBSI in the whole cohort were solid tumor, chronic kidney disease and carrying a port reservoir. Carrying a port reservoir was also a risk factor in patients with STs. Health-care acquisition was identified as a risk factor for GN CRBSI in the whole cohort, as well as in patients with STs and HMs. Inadequate empirical antibiotic treatment (IEAT) occurred regardless of the etiology: 49% for GNs and 48.6% for GPs (p = 0.96). In GP CRBSI, IEAT was mainly due to inadequate coverage against CoNS (87%), whereas in GN CRBSI, IEAT was associated with multidrug resistance (54.2%). Early (48 h and 7-day) and 30-day case-fatality rates were similar when analyzed according to the type of underlying disease and etiology, except for the 30-day case-fatality rate, which was higher in the group of patients with STs compared to those with HMs (21.5% vs. 12.5%, p = 0.027). The 48 h case-fatality rate was significantly higher in patients in whom the catheter had not been removed (5.6% vs. 1%; p = 0.011), and it remained significant for GP CRBSI (6% vs. 1.3%, p = 0.023). Conclusions: GNs are an increasing cause of CRBSI in cancer patients, particularly in solid tumor patients carrying port reservoirs. Multidrug resistance among GNs is also increasing and is associated with higher rates of IEAT. Decreased 48 h survival was associated with the non-removal of the catheter. These findings should be considered when deciding on early therapeutic management for cancer patients with suspected CRBSI.

Inappropriate empirical antimicrobial treatment in bloodstream infections patients in the era of multidrug resistance

Background and objectives: Bloodstream infection (BSI) by multidrug-resistant Pseudomonas aeruginosa is a severe infection. This study aimed to evaluate and identify the predictors of mortality in patients who had bloodstream infection by carbapenem-resistant P. aeruginosa. Methods: This is a retrospective cohort study, approved by Committee of Ethics in Research with Human Participants, which included 87 consecutive patients hospitalized in a referral hospital in Brazil. Clinical and demographic information about each patient were obtained from hospital records. The Student’s T-test was used to compare continuous variables and x2 or Fisher’s exact tests to compare categorical variables. To determine independent risk factors for 30-day mortality, a multiple logistic regression model was used. A survival curve was constructed using the Kaplan–Meier method. Results: Among the patients, 87.3% use antibiotics previously, 60.9% received inadequate empirical treatment, and the 30-day mortality rate was 57.5%. Inappropriate antibiotic empirical therapy was independently associated with a 30-days death and mortality rate. Conclusion: These findings can show some insights about the relationship between higher mortality and inappropriate empirical therapy for patients with BSI by P. aeruginosa. There is a need for better diagnostic tests and infection control programs should focus on de-escalation the antibiotic inappropriate therapy, mainly in BSI caused by carbapenem-resistant P. aeruginosa.

Clinical characteristics, aetiology and mortality/recurrence risk factors of acute cholangitis in patients with and without biliary stent

ObjectivesAcute cholangitis is one of the most frequent complications in patients carrying biliary stents. The aim of our study is to analyze the demographic and clinical characteristics, as well as the microbiological profile and evolution of patients with acute bacteremic cholangitis, comparing them based upon they were or not biliary stent carriers. MethodsWe performed a retrospective analysis of all consecutive patients over 18 years-old with a stent placement in our center between 2008 and 2017 were included. We compared them with our prospective cohort of patients with a diagnosis of acute bacteremic cholangitis. Primary outcome was 30-day mortality. Secondary outcome was clinical cure at day 7, 14-day mortality and 90-day recurrence. ResultsTwo hundred and seventy-three patients were analyzed, including 156 in the stent-related (SR) and 117 in the stent not-related (SNR) group, respectively. Stent-related colangitis patients were younger, with more comorbidities and with a greater severity of infection. Escherichia coli and Klebsiella pneumonia were the most frequent isolation. Enterococcus spp. was the third most frequent isolation in SR group but were uncommon in SNR patients; where E. coli was the most prevalent microorganism. Septic shock (HR 3.44, 95% [CI 1.18–8.77]), inadequate empirical treatment (HR 2.65, 95% CI [1.38–.7.98]) and advanced neoplasia (HR 2.41, 95% CI [1.55–6.44]) were independent 30-day mortality risk factors. The 90-day recurrence rate significantly higher in those patients with stent-related cholangitis (29% vs. 13%, p=0.016) and stent replacement was associated with lower recurrence rate (HR 0.38, 95% CI [0.11–0.77]). ConclusionsClinical and microbiological profile, as well as outcome of patients with SR and SNR cholangitis were different. In SR group, recurrence rate was high and stent replacement was associated with a lower risk.

Pielonefritis en el anciano hospitalizado: uso de un antibiótico habitual y la adecuación a las guías

IntroductionPyelonephritis in the elderly present high incidence and morbidity-mortality. The increase in resistance makes good empirical handling essential. MethodsRetrospective observational study in people over 65 years old admitted during 2012-2017 to Palencia and Salamanca hospitals with a diagnosis of pyelonephritis. Inadequate empirical antibiotic treatment was defined if it conformed to the indications of the SEIMC Guide (2016). Results292 episodes, mean age 82±10 years, 48.3% male. Escherichia coli 53.8% and Klebsiella spp 8. 9% were the most frequently microbiological isolation found. 180 episodes (61.6%) received inadequate empirical treatment. The two most frequent causes were the use of antibiotics not included in the guidelines 107 (59.5%) and the use of 2nd-3rd generation cephalosporins in patients with risk factors for Extended spectrum betalactamases 63 (35%). Absence of identification of risk factors of extended-spectrum betalactamases was found associated to inadequate empirical antibiotic treatment (p<0,05). Inadequate treatment did not increase mortality (p>0.05). ConclusionsThe adequacy of antibiotic use in the elderly admitted for pyelonephritis according to the SEIMC Guidelines is low. The lack of identification of risk factors for betalactamases-producing Enterobacteriacea was the main factor involved. Inadequate empirical treatment was not associated with increased mortality.

A Large Multicenter Prospective Study of Community-Onset Healthcare Associated Bacteremic Urinary Tract Infections in the Era of Multidrug Resistance: Even Worse than Hospital Acquired Infections?

IntroductionHealthcare-associated (HCA) infections represent a growing public health problem. The aim of this study was to compare community-onset healthcare associated (CO-HCA) bacteremic urinary tract infections (BUTI) and hospital-acquired (HA)-BUTI with special focus on multidrug resistances (MDR) and outcomes.MethodsITUBRAS-project is a prospective multicenter cohort study of patients with HCA-BUTI. All consecutive hospitalized adult patients with CO-HCA-BUTI or HA-BUTI episode were included in the study. Exclusion criteria were: patients < 18 years old, non-hospitalized patients, bacteremia from another source or primary bacteremia, non-healthcare-related infections and infections caused by unusual pathogens of the urinary tract. The main outcome variable was 30-day all-cause mortality with day 1 as the first day of positive blood culture. Logistic regression was used to analyze factors associated with clinical cure at hospital discharge and with receiving inappropriate initial antibiotic treatment. Cox regression was used to evaluate 30-day all-cause mortality.ResultsFour hundred forty-three episodes were included, 223 CO-HCA-BUTI. Patients with CO-HCA-BUTI were older (p < 0.001) and had more underlying diseases (p = 0.029) than those with HA-BUTI. The severity of the acute illness (Pitt score) was also higher in CO-HCA-BUTI (p = 0.026). Overall, a very high rate of MDR profiles (271/443, 61.2%) was observed, with no statistical differences between groups. In multivariable analysis, inadequate empirical treatment was associated with MDR profile (aOR 3.35; 95% CI 1.77–6.35), Pseudomonas aeruginosa (aOR 2.86; 95% CI 1.27–6.44) and Charlson index (aOR 1.11; 95% CI 1.01–1.23). Mortality was not associated with the site of acquisition of the infection or the presence of MDR profile. However, in the logistic regression analyses patients with CO-HCA-BUTI (aOR 0.61; 95% CI 0.40–0.93) were less likely to present clinical cure.ConclusionThe rate of MDR infections was worryingly high in our study. No differences in MDR rates were found between CO-HCA-BUTI and HA-BUTI, in the probability of receiving inappropriate empirical treatment or in 30-day mortality. However, CO-HCA-BUTIs were associated with worse clinical cure.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-021-00537-0.

Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) for the Identification of Bacteria Causing Urinary Tract Infections

Background: Matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) technology is a technique which allows microbial identification in clinical microbiology laboratories based on microbial protein profiles. A promising application of the MALDI-TOF technique comprises carrying out identification from direct urine samples. Objectives: The aim of this study is to evaluate the performance of MALDI-TOF MS system for the rapid identification of clinically relevant urinary tract pathogens in urine samples to the species level. Methodology: two hundred (200) urine samples with findings suggestive of urinary tract infections (UTI) were identified directly by MALDI-TOF MS, and same samples were identified from culture on MALDI-TOF MS. 73 colonies from 73 samples were further identified by Bd Phoneix and PCR. Results: MALDI-TOF MS directly from samples identified 174 samples (91 to the species level 83 to genus level), while MALDI-TOF MS after culture identified 191 samples (187 to the level of species, and 4 to genus level). In addition, 9 samples gave no results from the direct method and no growth in culture. The sensitivity and specificity of direct method compared to after culture method was 91.1% and 100%, respectively. Colonies of 73 samples were detected by the BD Phoneix automated identification system and by PCR. The results were identical among the three systems. Conclusion: The ability of MALDI-TOF MS’s to detect microorganisms from urine samples directly can provide early diagnosis of UTIs and avoid the inadequate or unnecessary empirical antimicrobial treatment.

Trauma and Antimicrobial Resistance Are Independent Predictors of Inadequate Empirical Antimicrobial Treatment of Ventilator-Associated Pneumonia in Critically Ill Patients.

Background: We aimed to assess independent risk factors for inadequate initial antimicrobial treatment (IAT) in critically ill patients with ventilator-associated pneumonia (VAP) treated in intensive care units (ICU) and to determine whether IAT is associated with adverse outcomes in patients with VAP. Patients and Methods: A prospective cohort study was performed and included 152 patients with VAP treated in an ICU for more than 48 hours. The main outcomes of interest were all-cause ICU mortality and VAP-related mortality. Other outcomes considered were: intra-hospital mortality, VAP-related sepsis, relapse, re-infection, length of stay in ICU (ICU LOS), and number of days on mechanical ventilation (MV). Results: One-third of patients (35.5%) received inadequate antimicrobial therapy. Trauma (odds ratio [OR], 3.55; 95% confidence interval [CI], 1.25-10.06) and extensively drug-resistant (XDR) causative agent (OR, 3.09; 95% CI, 1.23-7.74) were independently associated with inadequate IAT. Inadequate IAT was associated with a higher mortality rate (OR, 3.08; 95% CI, 1.30-7.26), VAP-related sepsis (OR, 2.39; 95% CI, 1.07-5.32), relapse (OR, 3.25; 95% CI, 1.34-7.89), re-infection (OR, 6.06; 95% CI, 2.48-14.77), and ICU LOS (β 4.65; 95% CI, 0.93-8.36). Acinetobacter spp., Pseudomonas aeruginosa and Klebsiella/Enterobacter spp. were the most common bacteria in patients with IAT and those with adequate antimicrobial therapy. Conclusions: This study demonstrated that inadequate IAT is associated with a higher risk of the majority of adverse outcomes in patients with VAP treated in ICUs. Trauma and XDR strains of bacteria are independent predictors of inadequate IAT of VAP in critically ill patients.

184. Seven vs. 14 Days Treatment Duration for Afebrile Men with Urinary Tract Infections; A Randomized Clinical Trial

BackgroundTrials show that shorter-duration therapy is effective for many infectious diseases, but the optimal duration for UTI in men is unknown. Observational data suggests shorter-duration performs as well as longer-duration therapy, but trial data shows men with febrile UTI (a small but important subset of patients) do worse with 7 vs. 14 days of therapy. We performed a randomized controlled trial of afebrile men with UTI to determine whether 7 days of treatment was non-inferior to 14 days.MethodsMen with symptomatic UTI at 2 VA hospitals were enrolled. Inclusion criteria included male gender, outpatient treatment, prescribed 7 to 14 days of ciprofloxacin or trimethoprim/sulfamethoxazole, and new onset of at least 1 of: dysuria, frequency, urgency, hematuria, costovertebral angle tenderness, and perineal, flank, or suprapubic pain. Exclusion criteria included UTI treatment in the past 14 days, symptoms due to a non-UTI diagnosis, and inadequate empiric treatment. Enrolled subjects took their clinically-prescribed medications days 1–7, then study medication days 8–14. Study medications were placebo or the originally prescribed antimicrobial, different in appearance from the original medication. The primary outcome was percentage of subjects with symptom resolution 14 days after completion of active therapy. Secondary outcomes included recurrence of UTI and adverse events. A pre-specified minimally clinically significant difference of 10% was selected, with a P value of 0.05 considered to be significant. Primary analysis was per-protocol; intention-to-treat performed as secondary analysis.ResultsEnrollment totaled 273, with 272 randomized to 7 (n = 136) vs. 14 (n = 136) days of antimicrobials. Mean age was 67.8 (SD 11.6), with a mean Charlson comorbidity index of 1.3 (SD 1.6). Overall, 254 subjects were in the per-protocol analysis. Symptom resolution occurred in 122 of 131 (93.1%) subjects receiving 7 days treatment, and 111 of 123 (90.2%) receiving 14 days (difference 2.9%, 95% CI -4.7 to 10.5% P = .50), confirming non-inferiority. Intention-to-treat analysis (n = 272) showed similar results.ConclusionTreatment with 7 days of antimicrobials was non-inferior to 14 days for symptom resolution. Afebrile men with UTI should not be treated beyond 7 days.Disclosures All Authors: No reported disclosures

Clinical characteristics, aetiology and mortality/recurrence risk factors of acute cholangitis in patients with and without biliary stent

ObjectivesAcute cholangitis is one of the most frequent complications in patients carrying biliary stents. The aim of our study is to analyze the demographic and clinical characteristics, as well as the microbiological profile and evolution of patients with acute bacteremic cholangitis, comparing them based upon they were or not biliary stent carriers. MethodsWe performed a retrospective analysis of all consecutive patients over 18 years-old with a stent placement in our center between 2008 and 2017 were included. We compared them with our prospective cohort of patients with a diagnosis of acute bacteremic cholangitis. Primary outcome was 30-day mortality. Secondary outcome was clinical cure at day 7, 14-day mortality and 90-day recurrence. ResultsTwo hundred and seventy-three patients were analyzed, including 156 in the stent-related (SR) and 117 in the stent not-related (SNR) group, respectively. Stent-related colangitis patients were younger, with more comorbidities and with a greater severity of infection. Escherichia coli and Klebsiella pneumonia were the most frequent isolation. Enterococcus spp. was the third most frequent isolation in SR group but were uncommon in SNR patients; where E. coli was the most prevalent microorganism. Septic shock (HR 3.44, 95% [CI 1.18–8.77]), inadequate empirical treatment (HR 2.65, 95% CI [1.38–.7.98]) and advanced neoplasia (HR 2.41, 95% CI [1.55–6.44]) were independent 30-day mortality risk factors. The 90-day recurrence rate significantly higher in those patients with stent-related cholangitis (29% vs. 13%, p=0.016) and stent replacement was associated with lower recurrence rate (HR 0.38, 95% CI [0.11–0.77]). ConclusionsClinical and microbiological profile, as well as outcome of patients with SR and SNR cholangitis were different. In SR group, recurrence rate was high and stent replacement was associated with a lower risk.

Characteristics and Outcomes of Staphylococcus aureus Bloodstream Infection Originating From the Urinary Tract: A Multicenter Cohort Study.

Background Staphylococcus aureus bloodstream infection (SABSI) arising from a urinary tract source (UTS) is poorly understood.MethodsWe conducted a retrospective analysis in 3 major teaching hospitals in Spain of prospectively collected data of hospitalized patients with SABSI. SABSI-UTS was diagnosed in patients with urinary tract symptoms and/or signs, no evidence of an extra-urinary source of infection, and a urinary S. aureus count of ≥105 cfu/mL. Susceptibility of S. aureus strains and patient mortality were compared between SABSI from UTS (SABSI-UTS) and other sources (SABSI-other).ResultsOf 4181 episodes of SABSI, we identified 132 (3.16%) cases of SABSI-UTS that occurred predominantly in patients who were male, had high Charlson comorbidity scores, were dependent for daily life activities, and who had undergone urinary catheterization and/or urinary manipulation before the infection. SABSI-UTS was more often caused by MRSA strains compared with SABSI-other (40.9% vs 17.5%; P < .001). Patients with SABSI-UTS caused by MRSA more often received inadequate empirical treatment compared with those caused by susceptible strains (59.7% vs 23.1%; P < .001). The 30-day case fatality rate was lower in patients with SABSI-UTS than in those with SABSI-other (14.4% vs 23.8%; P = .02). Factors independently associated with mortality were dependence for daily activities (aOR, 3.877; 95% CI, 1.08–13.8; P = .037) and persistent bacteremia (aOR, 7.88; 95% CI, 1.57–39.46; P = .012).ConclusionsSABSI-UTS occurs predominantly in patients with severe underlying conditions and in those who have undergone urinary tract manipulation. Moreover, it is frequently due to MRSA strains and causes significant mortality.

Mortality after Delay of Adequate Empiric Antimicrobial Treatment of Bloodstream Infection.

Background: Timely empiric antimicrobial therapy is one of the cornerstones of the management of suspected bloodstream infection (BSI). However, studies about the effects of empiric therapy on mortality have reported inconsistent results. The objective of this study was to estimate the effect of delay of appropriate empiric therapy on early mortality in patients with BSI. Methods: Data for the propensity score matching (PSM) study were obtained from a cohort of patients with BSI. Inadequate empiric treatment was defined as in vitro resistance to the antimicrobial regimen administered <6 h after blood cultures were taken. The primary outcome measure was 14-day mortality. Thirty-day mortality and median length of stay (LOS) were secondary outcomes. PSM was applied to control for confounding. Results: Of a total of 893 included patients with BSI, 35.7% received inadequate initial empiric treatment. In the PSM cohort (n = 334), 14-day mortality was 9.6% for inadequate antibiotic treatment, compared to. 10.2% in adequate empiric treatment (p = 0.85). No prolonged median LOS was observed in patients who initially received inadequate therapy (10.5 vs. 10.7 days, p = 0.89). Conclusions: In this study, we found no clear effect of inadequate empirical treatment on mortality in a low-risk BSI population. The importance of early empiric therapy compared to other determinants, may be limited. This may not apply for specific subpopulations, e.g., patients with sepsis.

Characteristics of febrile urinary tract infections in older male adults

BackgroundUrinary tract infections (UTI) are among the most frequent bacterial infections in older adults. The aim of the study was to analyse the existence of differences in clinical features, microbiological data and risk of infection by multidrug-resistant organisms (MDRO) between older and non-older men with febrile UTI (FUTI).MethodsThis was an ambispective observational study involving older males with a FUTI attended in the Emergency Department. Variables collected included age, comorbidity, diagnostic of healthcare-associated (HCA)-FUTI, clinical manifestations, hospitalization, mortality, and microbiological data.ResultsFive hundred fifty-two males with a FUTI, 329 (59.6%) of whom were older adults, were included. Older males had a higher frequency of HCA-FUTI (p < 0.001), increased Charlson scores (p < 0.001), had received previous antimicrobial treatment more frequently (p < 0.001) and had less lower urinary tract symptoms (p < 0.001). Older patients showed a lower frequency of FUTI caused by E. coli (p < 0.001) and a higher rate of those due to Enterobacter spp. (p = 0.003) and P. aeruginosa (p = 0.033). Resistance rates to cefuroxime (p = 0.038), gentamicin (p = 0.043), and fluoroquinolones (p < 0.001) in E. coli isolates and the prevalence of extended-spectrum beta-lactamase and AmpC producing E. coli and Klebsiella spp. strains (p = 0.041) and MDRO (p < 0.001) were increased in older males. Inadequate empirical antimicrobial treatment (p = 0.004), frequency of hospitalization (p < 0.001), and all cause in-hospital mortality (p = 0.007) were higher among older patients. In the multivariate analysis, being admitted from an long term care facility (OR 2.4; 95% CI: 1.06–5.9), having a urinary tract abnormality (OR 2.2; 95% CI: 1.2–3.8) and previous antimicrobial treatment (OR 3.2; 95% CI: 1.9–5.4) were associated to FUTI caused by MDRO.ConclusionsOlder male adults with a FUTI have different clinical characteristics, present specific microbiological features, and antimicrobial resistance rates. In the multivariate analysis being an older male was not associated with an increased risk of FUTI caused by MDRO.

Inadequate empirical antimicrobial treatment in older people with bacteremic urinary tract infection who reside in nursing homes: A multicenter prospective observational study.

The aim of the study was to determine the rate of inadequate empirical antimicrobial treatment in older nursing home residents with bacteremic urinary tract infection and its influence on prognosis. We carried out a multicentric prospective observational study in five Spanish hospitals. Patients aged >65 years with pyelonephritis or urinary sepsis with bacteremia were included. Clinical characteristics, the percentage of inadequate empirical antibiotic treatment, length of hospital stay and mortality were evaluated. A total of 181 patients, 54.7% women, were included in the study, and 35.9% of the patients came from nursing homes. These patients had higher percentages of ultimately or rapidly fatal disease (92.3% vs 53.4%; P < 0.001), were older (83.15 ± 6.97 years vs 79.34 ± 7.25 years; P = 0.001) and had higher Acute Physiology And Chronic Health Evaluation II (28.38 ± 8.57 vs 19.83 ± 5.88). The percentage of extended-spectrum beta-lactamases was higher in patients from nursing homes (30.6% vs 16.3%; P = 0.045), as was the percentage of inadequate empirical antibiotic treatment (40% vs 20.7%; P = 0.005). Length of hospital stay was longer (10.82 ± 3.62 days vs 9.04 ± 4.88 days; P < 0.001). However, 30-day mortality was not related to nursing home by multivariate analysis (OR 1.905, 95% CI 0.563-6.446; P = 0.300). Nursing home patients with bacteremic urinary tract infections had a higher rate of extended-spectrum beta-lactamase-producing enterobacteriacea and inadequate empirical antimicrobial treatment. Clinicians should consider these findings and avoid inappropriate antimicrobial agents for empirical treatment. Geriatr Gerontol Int 2019; 19: 1112-1117.

Infections related to healthcare in patients hospitalized in a Urology service: Resistance patterns and adequacy of empirical antibiotic treatment as a prognostic factor

ObjectivesTo evaluate the suitability of empirical antibiotic therapy in HAIs and the antibiotic resistance patterns of the responsible microorganisms, as well as the incidence of mortality and risk factors involved. MethodA prospective observational study was carried out on patients of both sexes older than 16years, admitted by any urological process during a period of 4years. The incidence and characteristics of HAIs, as well as the causative organism and its resistance, the initial empirical antibiotic therapy and its modification, if required, and mortality rates are analyzed. ResultsOut of 6546 patients, 6.3% suffered HAIs, 70.5% corresponding to urinary tract infection and 22.1% to infection of the surgical wound. E.coli, Enterococcus spp., Klebsiella spp. y P.aeruginosa were the most frequently implicated (25.1%, 17.5%, 13.5% and 12.3%, respectively). E.coli and Klebsiella spp. were producers of extended-spectrum beta-lactamases (ESBL) in 24.7% and 47.8%, respectively. 4.3% of Klebsiella and 33.3% of Pseudomonas were carbapenems-resistant. The overall resistance to quinolones was approximately 50%. The most commonly used antibiotics for empirical therapy were cephalosporins of 3rd and 4th generation (33.6%) and carbapenems (28.2%). An overall rate of adequacy of empirical antibiotic therapy of 82.9% was obtained. The mortality rate in patients with HAIs was 2.2%, compared with 0.3% in patients without infection. In a multivariate analysis, the variables associated with the highest mortality risk were the isolation of ESBL-producing enterobacteria and the inadequate empirical antibiotic treatment. ConclusionsThe selection of empirical antibiotic therapy was quite accurate. An increase in HAIs by multiresistant microorganisms, such as ESBL Enterobacteria or multiresistant P.aeruginosa is being observed. The mortality risk increases with inadequate initial empirical antibiotic therapy or when the responsible microorganism is an ESBL enterobacteria.

Prediction of bloodstream infection caused by extended-spectrum β-lactamase-producing Enterobacterales in patients with suspected community-onset sepsis

In severe infections, time to appropriate therapy is decisive for survival. Patients with bloodstream infection caused by extended-spectrum β-lactamase-producing Enterobacterales (EPE-BSI) often receive inadequate empirical treatment. This study aimed to identify risk factors, to evaluate a previously suggested risk score and to suggest a new score for facilitating empirical treatment choice. Predictors for EPE-BSI were assessed through a retrospective case-control design. The diagnostic performance of the two scores was evaluated. Included patients had blood cultures sampled at four EDs in Stockholm (2012-2015), were admitted, and received antibiotics with activity against Gram-negative bacilli. A total of 277 EPE-BSI cases and 400 controls were included. The strongest predictor of EPE-BSI was prior EPE-positive culture (cases 33% vs. controls 3%; multivariate (MV) OR = 19.1). Recent EPE-positivity within ≤3 months had a univariate OR of 32.8. Other major predictors were recent prostate biopsy (14% vs. 1%; MV OR = 22.2) and healthcare abroad (6% vs. 2%; MV OR = 3.9). Several previously suggested risk factors were not associated with EPE-BSI. The previously developed Utrecht score had a sensitivity of 54% and a specificity of 77%. The Stockholm score suggested herein (prior EPE-positive culture/prostate biopsy/healthcare abroad) showed comparable sensitivity (50%) but better specificity (96%). Prediction in patients lacking major predictors was difficult and caused high false-positive rates, which would cause unnecessary overtreatment. Prior EPE-positive culture, especially recently sampled, prostate biopsy and healthcare abroad were the strongest risk factors for community-onset EPE-BSI in Stockholm. Local data are needed when evaluating risk-scoring models before implementation.

Salvage Strategy for Long-Term Central Venous Catheter-Associated Staphylococcus aureus Infections in Children.

Introduction: Current international guidelines strongly recommend catheter removal in case of S. aureus central line-associated bloodstream infection (CLASBI), but a catheter salvage strategy may be considered in children given age-related specificities. No data is available regarding the outcome of this strategy in children. This study aims to evaluate catheter salvage strategy in children with S. aureus CLABSI, and to determine treatment failure rates and associated risk factors.Methods: We retrospectively analyzed data for all children <18 years having S. aureus CLABSI on a long-term central venous catheter in a tertiary hospital from 2010 to 2014. We defined catheter salvage strategy as a central venous catheter left in place ≥3 days after initiation of empiric treatment for suspected bacteremia, and catheter salvage strategy failure as the persistence or relapse of bacteremia with a S. aureus strain harboring the same antibiotic susceptibility pattern, or the occurrence or the worsening of local or systemic infectious complication between 72 h and 28 days after the first positive blood culture.Results: During the study period, 49 cases of S. aureus CLABSI on long-term central venous catheters were observed in 41 children (including 59% with long-term parenteral nutrition) and 6 (15%) isolates were resistant to methicillin. A catheter salvage strategy was chosen in 37/49 (76%) cases and failed in 12/37 (32%) cases. Initial presence of bloodstream co-infection, serum concentration of vancomycin under the targeted value and inadequate empiric treatment were significantly associated with catheter salvage therapy failure.Conclusions: The catheter salvage strategy of S. aureus CLABSI on a long-term central venous catheter was frequent in the studied hospital and failed only in one third of cases.

Polymyxin B clinical outcomes: A prospective study of patients undergoing intravenous treatment.

Polymyxins, especially polymyxin B, has become the last line of therapy against Gram-negative pathogens' carbapenemase producers. However, given increasing use of polymyxin B in clinical settings its therapeutic value has been evaluated worldwide due to its toxic effects. The aim of this study was to assess the efficacy and safety of antimicrobial therapy with polymyxin B in patients with multidrug-resistant bacteria in Brazil. This was a prospective cohort study in a 403-bed academic tertiary care centre, located in the countryside of Brazil. Patients receiving polymyxin B intravenous treatment for at least 72hours were eligible for the study. Antimicrobial susceptibility, adverse reactions and clinical outcomes were submitted for descriptive analysis. Main outcomes measure the following: Patients' conditions following treatment (Treatment Success, Mortality, Treatment Failure, Inadequate Empiric Treatment or Indeterminate Response) and toxicities induced by polymyxin B (nephrotoxicity and skin hyperpigmentation). Among 247 patients, treatment success was achieved in 25.1%, while mortality was observed in 32.8%. Empirical therapy was prescribed for 26.3% of the patients. Nephrotoxicity was reported in 40.5%. The carbapenemase producer, Klebsiella pneumonia, was the bacterium most associated with mortality (22.2%). Even though polymyxin B is currently the main therapy against carbapenemase producers, its use demands robust criteria to lead to positive clinical outcomes.