Modelos predictivos de bacteriemia en el servicio de urgencias: revisión sistemática / Models to predict bacteremia in the emergency department: a systematic review

Objetivo. La obtención de hemocultivos (HC) se realiza en el 15% de los pacientes atendidos con sospecha de infección en los servicios de urgencias (SU) con una rentabilidad diagnóstica variable (2-20%). La mortalidad a 30 días de estos pacientes con bacteriemia es elevada, doble o triple que el resto con el mismo proceso. Así, encontrar un modelo predictivo de bacteriemia eficaz y aplicable en los SU sería muy importante. Clásicamente, el modelo de Shapiro ha sido la referencia en todo el mundo. El objetivo de esta revisión sistemática (RS) es comparar la capacidad para predecir bacteriemia en los SU de los distintos modelos predictivos publicados desde el año 2008 (fecha de publicación del modelo de Shapiro). Métodos. Se realiza una RS siguiendo la normativa PRISMA en las bases de datos de PubMed, Web of Science, EMBASE, Lilacs, Cochrane, Epistemonikos, Tripdatabase y ClinicalTrials.gov desde enero de 2008 hasta 31 mayo 2023 sin restricción de idiomas y utilizando una combinación de términos MESH: “Bacteremia/Bacteraemia/Blood Stream Infection”, “Prediction Model/Clinical Prediction Rule/Risk Prediction Model”, “Emergencies/Emergency/Emergency Department” y “Adults”. Se incluyeron estudios de cohortes observacionales (analíticos de rendimiento diagnóstico). Para valorar la calidad del método empleado y el riesgo de sesgos de los artículos incluidos se utilizó la NewcastleOttawa Scale (NOS). No se incluyeron estudios de casos y controles, revisiones narrativas y en otros tipos de artículos. No se realizaron técnicas de metanálisis, pero los resultados se compararon narrativamente. El protocolo de la RS se registró en PROSPERO (CRD42023426327). Resultados. Se identificaron 917 artículos y se analizaron finalmente 20 que cumplían los criterios de inclusión. Los estudios incluidos contienen 33.182 HC procesados con 5.074 bacteriemias (15,3%). Once estudios fueron calificados de calidad alta, 7 moderada y 2 baja... (AU)

Objective. Blood cultures are ordered in emergency departments for 15% of patients with suspected infection. The diagnostic yield varies from 2% to 20%. Thirty-day mortality in patients with bacteremia is high, doubling or tripling the rate in patients with the same infection but without bacteremia. Thus, finding an effective model to predict bacteremia that is applicable in emergency departments is an important goal. Shapiro’s model is the one traditionally used as a reference internationally. The aim of this systematic review was to compare the predictive power of bacteremia risk models published since 2008, when Shapiro’s model first appeared. Methods. We followed the recommendations of the Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA) statement, searching in the following databases for articles published between January 2008 and May 31, 2023: PubMed, Web of Science, EMBASE, Lilacs, Cochrane, Epistemonikos, Trip Medical Database, and ClinicalTrials.gov. No language restrictions were specified. The search terms were the following Medical Subject Headings: bacteremia/bacteraemia/blood stream infection, prediction model/clinical prediction rule/risk prediction model, emergencies/emergency/emergency department, and adults. Observational cohort studies analyzing diagnostic yield were included; case-control studies, narrative reviews, and other types of articles were excluded. The Newcastle-Ottawa Scale was used to score quality and risk of bias in the included studies. The results were compared descriptively, without meta-analysis. The protocol was included in the PROSPERO register (CRD42023426327). Results. Twenty studies out of a total of 917 were found to meet the inclusion criteria. The included studies together analyzed 33 182 blood cultures, which detected 5074 cases of bacteremia (15.3%). Eleven studies were of high quality, 7 of moderate quality, and 2 of low quality... (AU)

Bacteriophage and antibiotic combination therapy for recurrent Enterococcus faecium bacteremia.

Enterococcus faecium is a member of the human gastrointestinal (GI) microbiota but can also cause invasive infections, especially in immunocompromised hosts. Enterococci display intrinsic resistance to many antibiotics, and most clinical E. faecium isolates have acquired vancomycin resistance, leaving clinicians with a limited repertoire of effective antibiotics. As such, vancomycin-resistant E. faecium (VREfm) has become an increasingly difficult to treat nosocomial pathogen that is often associated with treatment failure and recurrent infections. We followed a patient with recurrent E. faecium bloodstream infections (BSIs) of increasing severity, which ultimately became unresponsive to antibiotic combination therapy over the course of 7 years. Whole-genome sequencing (WGS) showed that the patient was colonized with closely related E. faecium strains for at least 2 years and that invasive isolates likely emerged from a large E. faecium population in the patient's gastrointestinal (GI) tract. The addition of bacteriophage (phage) therapy to the patient's antimicrobial regimen was associated with several months of clinical improvement and reduced intestinal burden of VRE and E. faecium. In vitro analysis showed that antibiotic and phage combination therapy improved bacterial growth suppression compared to therapy with either alone. Eventual E. faecium BSI recurrence was not associated with the development of antibiotic or phage resistance in post-treatment isolates. However, an anti-phage-neutralizing antibody response occurred that coincided with an increased relative abundance of VRE in the GI tract, both of which may have contributed to clinical failure. Taken together, these findings highlight the potential utility and limitations of phage therapy to treat antibiotic-resistant enterococcal infections. IMPORTANCE: Phage therapy is an emerging therapeutic approach for treating bacterial infections that do not respond to traditional antibiotics. The addition of phage therapy to systemic antibiotics to treat a patient with recurrent E. faecium infections that were non-responsive to antibiotics alone resulted in fewer hospitalizations and improved the patient's quality of life. Combination phage and antibiotic therapy reduced E. faecium and VRE abundance in the patient's stool. Eventually, an anti-phage antibody response emerged that was able to neutralize phage activity, which may have limited clinical efficacy. This study demonstrates the potential of phages as an additional option in the antimicrobial toolbox for treating invasive enterococcal infections and highlights the need for further investigation to ensure phage therapy can be deployed for maximum clinical benefit.

Treatment Outcome of Severe Respiratory Type B Tularemia Using Fluoroquinolones.

BACKGROUND: Fluoroquinolones lack approval for treatment of tularemia but have been used extensively for milder illness. Here, we evaluated fluoroquinolones for severe illness. METHODS: In an observational study, we identified case-patients with respiratory tularemia from July to November 2010 in Jämtland County, Sweden. We defined severe tularemia by hospitalization for >24 hours and severe bacteremic tularemia by Francisella tularensis subsp. holarctica growth in blood or pleural fluid. Clinical data and drug dosing were retrieved from electronic medical records. Chest images were reexamined. We used Kaplan-Meier curves to evaluate time to defervescence and hospital discharge. RESULTS: Among 67 case-patients (median age, 66 years; 81% males) 30-day mortality was 1.5% (1 of 67). Among 33 hospitalized persons (median age, 71 years; 82% males), 23 had nonbacteremic and 10 had bacteremic severe tularemia. Subpleural round consolidations, mediastinal lymphadenopathy, and unilateral pleural fluid were common on chest computed tomography. Among 29 hospitalized persons with complete outcome data, ciprofloxacin/levofloxacin (n = 12), ciprofloxacin/levofloxacin combinations with doxycycline and/or gentamicin (n = 11), or doxycycline as the single drug (n = 6) was used for treatment. One disease relapse occurred with doxycycline treatment. Treatment responses were rapid, with median fever duration 41.0 hours in nonbacteremic and 115.0 hours in bacteremic tularemia. Increased age-adjusted Charlson comorbidity index predicted severe bacteremic tularemia (odds ratio, 2.7 per score-point; 95% confidence interval, 1.35-5.41). A 78-year-old male with comorbidities and delayed ciprofloxacin/gentamicin treatment died. CONCLUSIONS: Fluoroquinolone treatment is effective for severe tularemia. Subpleural round consolidations and mediastinal lymphadenopathy were typical findings on computed tomography among case-patients in this study.

Enzymatic debridement with bromelain and development of bacteremia in burn injuries: A retrospective cohort study.

BACKGROUND: Debridement is crucial for effective wound management in patients with severe burn injuries, and bromelain, a proteolytic enzyme from pineapple stems, has emerged as a promising alternative for surgery. However, potential links of bromelain use to fever and sepsis have raised some concerns. Given the uncertainty as to whether this was caused by infection or other inflammatory sources, we aimed to investigate if the use of topical bromelain was associated with bacteremia. METHODS: This single-centre retrospective cohort study included critically ill adult patients with severe burn injuries hospitalised at the Burn Center of the University Hospital Zurich between January 2017 and December 2021. Data were collected from two in-hospital electronic medical records databases. Our primary outcome, the association between topical bromelain treatment and the development of bacteremia, was investigated using a competing risk regression model, taking into account the competing risk of death. As a secondary outcome, the relationship between bromelain treatment and overall ICU mortality was examined using a Cox proportional hazards model. RESULTS: The study included 269 patients with a median age of 50 years and median burnt total body surface area of 19%. A first bacteremia occurred in 61 patients (23%) after a median time of 6 days. Bromelain treatment was given to 83 (31%) of patients, with 22 (27%) of these developing bacteremia. In the fully adjusted competing risk regression model, no evidence for an association between bromelain treatment and bacteremia was found (SHR 0.79, 95%CI 0.42-1.48, p = 0.47). During hospital stay, 40 (15%) of patients died. There was no significant difference in mortality between patients treated with bromelain and those who were not (HR 0.55, 95%CI 0.26-1.20, p = 0.14). Among the five multidrug-resistant (MDR) pathogens identified, three were found in patients with bromelain treatment. CONCLUSION: Our study did not confirm an association between topical bromelain and bacteremia in patients with severe burn injuries. This finding can inform evidence-based practices by addressing concerns about potential risks of bromelain use, contributing to the development of more effective and safe burn wound management strategies.

[Does a rapid antibiotic susceptibility test optimize antibiotic therapy of patients with bacteremia ?] / Un antibiogramme rapide optimise-t-il la prise en charge thérapeutique des patients présentant une bactériémie ?

BACKGROUND: We evaluated the contribution of a rapid antibiotic susceptibility test performed directly from a positive blood culture (PBC), the dRAST™, in the management of patients with bacteremia. METHODS: We retrospectively compared the time from sampling to availability of antibiotic susceptibility test (AST) results («time-to-result¼, TTR) between dRAST™ and classic AST (Vitek®2), in 150 patients with bacteremia. The antibiotic treatment of these 150 patients was classified into three categories (optimal, suboptimal, ineffective) according to the time of availability of AST results. RESULTS: Adaptation of antibiotic treatment to optimal therapy following AST results occurred in 46/100 (46 %) of Gram-negative PBC and in 4/50 (2 %) of Gram-positive HP. TTR was significantly lower with dRAST™ compared with classic AST (29:35 (± 08:48) hours versus 50:55 (± 12:45) hours, p < 0.001). CONCLUSION: For patients with bacteremia requiring adjustment of empirical antibiotic therapy based on AST, dRAST™ could allow a faster administration of optimal therapy.

CONTEXTE: Nous avons évalué la contribution d'un antibiogramme rapide réalisé directement à partir d'une hémoculture positive (HP), le dRAST™, dans la prise en charge des patients présentant une bactériémie. Méthodes: Nous avons comparé, rétrospectivement, le délai entre le prélèvement et la disponibilité des résultats d'antibiogramme («temps-pour-résultats¼, TPR) entre le dRAST™ et l'antibiogramme classique (Vitek®2), auprès de 150 patients présentant une bactériémie. Les antibiothérapies de ces 150 patients ont été classés en trois catégories (optimale, suboptimale, inefficace) en fonction du moment d'obtention des résultats de l'antibiogramme. Résultats : L'adaptation du traitement antibiotique en thérapie optimale suite au résultat de l'antibiogramme est survenue chez 46/100 (46 %) des HP à Gram négatif et chez 4/50 (2 %) des HP à Gram positif. Le TPR était significativement plus faible avec le dRAST™ par rapport à l'antibiogramme classique (29:35 (± 08:48) heures versus 50:55 (± 12:45) heures, p < 0,001). CONCLUSION: Pour les patients avec bactériémie nécessitant une adaptation de l'antibiothérapie empirique basée sur l'antibiogramme, le dRAST™ permettrait une administration plus rapide du traitement optimal.

Comparative analysis of a rapid diagnostic test and scoring tools for ESBL detection in Enterobacterales bloodstream infections for optimizing antimicrobial therapy.

IMPORTANCE: Our study addresses a significant issue in the medical and scientific community-the delayed administration of appropriate antimicrobial treatments due to the time-consuming process of phenotypic susceptibility data collection in gram-negative bloodstream infections. Our research indicates that a multiplex PCR rapid diagnostic test (RDT) significantly outperformed two clinical scoring tools in predicting ceftriaxone susceptibility. Multiplex PCR also led to reduced instances of undertreatment with ceftriaxone and minimized overtreatment with carbapenems. Furthermore, multiplex PCR demonstrated high sensitivity and specificity in predicting ceftriaxone susceptibility. The results of our study underscore the potential RDTs to reduce the time to appropriate antimicrobial therapy, leading to improved patient outcomes and reduced healthcare costs.

Identifying Effective Durations of Antibiotic Therapy for the Treatment of Carbapenem-resistant Enterobacterales Bloodstream Infections: A Multicenter Observational Study.

In a propensity-score-weighted cohort of 183 adults with carbapenem-resistant Enterobacterales bacteremia at 24 US hospitals, patients receiving short courses of active therapy (7-10 days, median 9 days) experienced similar odds of recurrent bacteremia or death within 30 days as those receiving prolonged courses of active therapy (14-21 days, median 14 days).

Carriage of multidrug-resistant carbapenemase-producing gram-negative bacteria in patients admitted to NHS Greater Glasgow and Clyde hospitals: Implications for treatment.

BACKGROUND: Infections caused by gram-negative carbapenemase-producing organisms (CPO) have become a global phenomenon. Screening of patients for CPO that was carried out at 48-h intervals enables early detection of carriers for infection control purposes and planning therapy. METHODS: We investigated the bacterial flora detected on screening, the enzymes that conferred resistance and the proportion of patients who developed bacteraemia with CPO and their therapy. RESULTS: In all, 27 patients had a positive screen for CPO. A small but significant (7.5%) proportion of patients were not detected on initial screening. Escherichia coli and Klebsiella were predominant. New-Delhi metallo ß-lactamase and oxacillin carbapenemases were the main enzymatic mechanisms of resistance. Four (14.8%) patients developed bacteraemia with CPO (30- and 90-day survival 100% and 75%, respectively). CONCLUSION: A single negative screen does not rule out colonisation. A significant proportion of patients colonised with CPO develop bacteraemia. Vigilance is needed to prevent the nosocomial spread of CPO.

Treatment outcomes with benzylpenicillin and non-benzylpenicillin antibiotics, and the performance of the penicillin zone-edge test versus molecular detection of blaZ in penicillin-susceptible Staphylococcus aureus (PSSA) bacteraemia.

OBJECTIVES: The blaZ gene encodes penicillinase, which inactivates penicillin. As there were reports on suboptimal sensitivity for the penicillin zone-edge test, a phenotypic method for blaZ detection, we investigated treatment outcomes in patients with penicillin-susceptible Staphylococcus aureus (PSSA) bacteraemia (phenotypically negative for penicillinase), subjecting isolates to molecular testing for blaZ retrospectively. PATIENTS AND METHODS: A retrospective cohort study was conducted on 121 patients with a first episode of PSSA bacteraemia from 1 January 2012 to 31 October 2015 at Tan Tock Seng Hospital (TTSH), Singapore. Patients were grouped into IV benzylpenicillin and non-benzylpenicillin groups. The primary outcome was overall treatment failure, defined as either 30 day all-cause mortality and/or 90 day relapse. The penicillin (P10) zone-edge test was repeated on archived PSSA isolates, concurrently with penicillin MIC determination via gradient diffusion and PCR for blaZ. RESULTS: Among 121 patients, 57 patients (47.1%) received IV benzylpenicillin as the predominant antibiotic. There was no significant difference in overall treatment failure between treatment with the benzylpenicillin [7/57 (12.3%)] versus non-benzylpenicillin groups [12/64 (18.8%)] (P = 0.33) or cloxacillin/cefazolin [6/37 (16.2%)] (P = 0.59). For 112 PSSA isolates available for testing, repeat penicillin zone-edge testing was negative for penicillinase production, corroborating previous results. A single PSSA isolate with a negative penicillin zone-edge test was found to be positive for blaZ. CONCLUSIONS: We found no differences in overall treatment failure between patients with PSSA bacteraemia treated with benzylpenicillin, anti-staphylococcal ß-lactams cefazolin/cloxacillin and other antimicrobials, when using the penicillin zone-edge test as the phenotypic method for blaZ screening.

Assessment of mortality-related risk factors and effective antimicrobial regimens for treatment of bloodstream infections caused by carbapenem-resistant Pseudomonas aeruginosa in patients with hematological diseases.

Background: Infections caused by carbapenem-resistant Pseudomonas aeruginosa (CRPA) are related to higher mortality. The objective of this study was to explore clinical outcomes of CRPA bacteremia, identify risk factors and also, compare the efficacy of traditional and novel antibiotic regimens. Methods: This retrospective study was conducted at a blood diseases hospital in China. The study included hematological patients who were diagnosed with CRPA bacteremia between January 2014 and August 2022. The primary endpoint was all-cause mortality at day 30. Secondary endpoints included 7-day and 30-day clinical cure. Multivariable Cox regression analysis was employed to identify mortality-related risk factors. Results: 100 patients infected with CRPA bacteremia were included and 29 patients accepted allogenic-hematopoietic stem cell transplantation. 24 received ceftazidime-avibactam (CAZ-AVI)-based therapy and 76 received other traditional antibiotics. 30-day mortality was 21.0%. Multivariable cox regression analysis showed neutropenia >7 days after bloodstream infections (BSI) (P=0.030, HR: 4.068, 95%CI: 1.146~14.434), higher Pitt bacteremia score (P<0.001, HR:1.824, 95%CI: 1.322~2.517), higher Charlson comorbidity index (P=0.01, HR: 1.613, 95%CI: 1.124~2.315) and bacteremia due to multidrug-resistant Pseudomonas aeruginosa (MDR-PA) (P=0.024, HR:3.086, 95%CI: 1.163~8.197) were identified as independent risk factors of 30-day mortality. After controlling for confounders, an additional multivariable cox regression analysis revealed definitive regimens containing CAZ-AVI were associated with lower mortality in CRPA bacteremia (P=0.016, HR: 0.150, 95%CI: 0.032~0.702), as well as in MDR-PA bacteremia (P=0.019, HR: 0.119, 95%CI: 0.020~0.709). Conclusions: For patients with hematological diseases and CRPA bacteremia, 30-day mortality rate was 21.0% (21/100). Neutropenia >7 days after BSI, higher Pitt bacteremia score, higher Charlson comorbidity index and bacteremia due to MDR-PA increased 30-day mortality. CAZ-AVI-based regimens were effective alternatives for bacteremia due to CRPA or MDR-PA.

Short course antibiotic treatment of Gram-negative bacteraemia (GNB5): a study protocol for a randomised controlled trial.

INTRODUCTION: Prolonged use of antibiotics is closely related to antibiotic-associated infections, antimicrobial resistance and adverse drug events. The optimal duration of antibiotic treatment for Gram-negative bacteremia (GNB) with a urinary tract source of infection is poorly defined. METHODS AND ANALYSIS: Investigator-initiated multicentre, non-blinded, non-inferiority randomised controlled trial with two parallel treatment arms. One arm will receive shortened antibiotic treatment of 5 days and the other arm will receive antibiotic treatment of 7 days or longer. Randomisation will occur in equal proportion (1:1) no later than day 5 of effective antibiotic treatment as determined by antibiogram. Immunosuppressed patients and those with GNB due to non-fermenting bacilli (Acinetobacter spp, Pseudomonas spp), Brucella spp, Fusobacterium spp or polymicrobial growth are ineligible.The primary endpoint is 90-day survival without clinical or microbiological failure to treatment. Secondary endpoints include all-cause mortality, total duration of antibiotic treatment, hospital readmission and Clostridioides difficile infection. Interim safety analysis will be performed after the recruitment of every 100 patients. Given an event rate of 12%, a non-inferiority margin of 10%, and 90% power, the required sample size to determine non-inferiority is 380 patients. Analyses will be performed on both intention-to-treat and per-protocol populations. ETHICS AND DISSEMINATION: The study is approved by the Danish Regional Committee on Health Research (H-19085920) and the Danish Medicines Agency (2019-003282-17). The results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.Gov:NCT04291768.

Time for a Change: Considering Vancomycin Alternatives for Pediatric Methicillin-Resistant Staphylococcus aureus Bacteremia.

Vancomycin remains the standard of care for treating methicillin-resistant Staphylococcus aureus (MRSA) bacteremia in pediatrics largely because no alternative antibiotic is definitively superior. Long-standing historical precedent and S. aureus' notable lack of vancomycin resistance are clear benefits, but vancomycin's use remains plagued by nephrotoxicity and the need for therapeutic drug monitoring, with inadequate consensus on how best to dose or monitor vancomycin in pediatrics. Daptomycin, ceftaroline, and linezolid are all promising alternatives, with improved safety relative to vancomycin. However, inadequate and variable efficacy data limit confidence in their use. Despite this, we contend that it is time for clinicians to reconsider vancomycin's place in clinical use. In this review, we summarize the supporting data for using vancomycin versus these other anti-MRSA antibiotics, present a framework for antibiotic decision-making that considers patient-specific factors, and discuss approaches to antibiotic selection for various etiologies of MRSA bacteremia. This review aims to help pediatric clinicians choose among the various treatment options for MRSA bacteremia, acknowledging that the optimal antibiotic choice is sometimes uncertain.

Evaluation of the meropenem dosage and administration schedule in patients with bacteremia initial therapy.

BACKGROUND: The standard meropenem (MEPM) regimen allowed by insurance in Japan is 0.5 g two or three times a day. Differences in dosages and administration schedules in Japan were evaluated. METHODS: Patients with bacteremia for whom MEPM was used as the initial treatment at our institution between 2016 and 2021 were included. We retrospectively investigated patients classified into two groups: those treated according to severe infections (high-dose groupand others (low-dose group). After propensity score matching, we compared the probability of achieving free drug blood levels above the minimum inhibitory concentration (MIC) in 24 h (%fT > MIC) and outcomes. RESULTS: The probability of 100% fT > MIC was significantly higher in the high-dose group (96.4% vs 74.5%, odds ratio [OR] = 0.3, 95% confidence interval [CI] = 0.2-0.4, P = < 0.001). Regarding outcomes, the 30-day mortality rate was significantly lower in the high-dose group (1.4% vs. 11.4%, OR = 8.0, 95% CI = 1.5-43.7, P = 0.019). CONCLUSIONS: To improve outcomes in patients with bacteremia treated with MEPM, support for appropriate antimicrobial use is necessary for compliance with the dosage and administration schedule according to severe infections in initial treatment.

Emerging issues on Staphylococcus aureus endocarditis and the role in therapy of daptomycin plus fosfomycin.

INTRODUCTION: Methicillin-resistant and -susceptible Staphylococcus aureus (MRSA/MSSA) infections are a major global health-care problem. Bacteremia with S. aureus exhibits high rates of morbidity and mortality and can cause complicated infections such as infective endocarditis (IE). The emerging resistance profile of S. aureus is worrisome, and several international agencies have appealed for new treatment approaches to be developed. AREAS COVERED: Daptomycin presents a rapid bactericidal effect against MRSA and has been considered at least as effective as vancomycin in treating MRSA bacteremia. However, therapy failure is often related to deep-seated infections, e.g. endocarditis, with high bacterial inocula and daptomycin regimens <10 mg/kg/day. Current antibiotic options for treating invasive S. aureus infections have limitations in monotherapy. Daptomycin in combination with other antibiotics, e.g. fosfomycin, may be effective in improving clinical outcomes in patients with MRSA IE. EXPERT OPINION: Exploring therapeutic combinations has shown fosfomycin to have a unique mechanism of action and to be the most effective option in preventing the onset of resistance to and optimizing the efficacy of daptomycin, suggesting the synergistic combination of fosfomycin with daptomycin is a useful alternative treatment option for MSSA or MRSA IE.

Risk factors for mortality after linezolid treatment of vancomycin-resistant Enterococcus bloodstream infection.

OBJECTIVES: We analyzed the risk factors affecting linezolid treatment outcome in vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI). METHODS: We conducted a multicenter observational study of patients who received linezolid 600 mg every 12 hours for VRE BSI. The primary outcome was 28-day mortality. The estimated area under the concentration-time curve and trough concentration were calculated. Multivariable logistic regression was used for the outcome analysis. RESULTS: A total of 170 patients were included: 114 (67.1%) survived and 56 (32.9%) did not. A total of 26 (18.2%) isolates showed a linezolid minimum inhibitory concentration (MIC) of ≤1 mg/l, 113 (79.0%) of 2 mg/l, and 4 (2.8%) of 4 mg/l. The univariable analysis showed that the linezolid MIC and concentration-time curve/MIC were not associated with mortality (P = 0.95 and P = 0.42, respectively). After adjusting for underlying comorbidity and disease severity, the linezolid dose per body weight (LDBW), body height, and interaction between them were independent risks for mortality. Marginal analysis showed that increasing the LDBW was protective in patients with a body height <160 cm. A trough concentration of >12.2 mg/l was a risk factor for thrombocytopenia. CONCLUSION: The LDBW and body height were interactively associated with clinical outcomes of linezolid treatment for VRE BSI.

Outcomes of Daptomycin Plus Ceftaroline Versus Alternative Therapy for Persistent Methicillin-resistant Staphylococcus aureus (MRSA) Bacteraemia.

OBJECTIVES: This study aimed to evaluate both efficacy and safety of combination therapy with daptomycin plus ceftaroline (DAP/CPT) versus alternative therapy in the treatment of persistent methicillin-resistant Staphylococcus aureus bacteraemia (MRSAB). METHODS: This retrospective, single-centre study investigated adult patients who underwent a change in antibiotic therapy for persistent MRSAB. Daptomycin plus ceftaroline was compared with alternative therapy after initial treatment with vancomycin or DAP monotherapy was modified. The primary outcome was in-hospital mortality, and several secondary efficacy and safety outcomes were evaluated. RESULTS: A total of 68 patients with persistent MRSAB had initial therapy switched to DAP/CPT (n = 43) or alternative therapy (n = 25). In-hospital mortality was similar with DAP/CPT versus alternative therapy (16.3% vs. 16%; P = 1.0). On average, the total duration of bacteraemia was numerically 1 day less in patients switched to DAP/CPT (11.4 days vs. 12.5 days; P = 0.5). Daptomycin plus ceftaroline was de-escalated in 81% of patients after receiving combination therapy for an average of 12.5 days. Secondary outcomes, including rates of adverse events and emergence of antimicrobial resistance, were similar between the two groups. CONCLUSIONS: Switching to DAP/CPT after approximately 1 week of persistent MRSA bacteraemia may result in similar clinical outcomes when compared with alternative therapy. Rates of adverse events and emergence of antimicrobial resistance were low without a statistically significant difference observed between DAP/CPT and alternative therapy. These findings, as well as the impact of earlier switch or prolonged treatment with the combination, require further investigation.

Efficacy and safety of intravenous fosfomycin for the treatment of carbapenem-resistant Klebsiella pneumoniae.

The aim of the study was to evaluate clinical and microbiological efficacy and safety of intravenous fosfomycin for the treatment of carbapenem-resistant K. pneumoniae infections. All adult inpatients receiving 48 h of intravenous fosfomycin, alone or combined with other antibiotics were included in the study. Overall favorable clinical response rate was 75.3% among 94 patients. Clinical response rates were 92.3%, 72.2% and 56.0% for urinary tract infections, bacteremia and pneumonia, respectively. Microbiological eradication was achieved in 55 of 86 patients. 30-day mortality was 33.0%. Adverse events were generally mild. Common adverse events were hypokalemia (37.2%) and hypernatremia (22.3%). Intravenous fosfomycin is an effective antibiotic option with a good safety profile for the treatment of carbapenem-resistant K. pneumoniae infections. The most favorable clinical and microbiological responses are obtained in urinary tract infections. The efficacy of the drug in more severe infections, such as pneumonia and bacteremia, is comparable to the literature.

The Clinical Evaluation of Third-generation Cephalosporins As Definitive Therapy for Enterobacter spp. and Klebsiella aerogenes Bacteremia.

Objective Third-generation cephalosporins (3GCs) may be susceptible in vitro to Enterobacter spp. and Klebsiella aerogenes. However, treatment with mainly fourth-generation cephalosporins or carbapenems is currently recommended. Diversification of antimicrobial agents in therapy is required to avoid the selection pressure of resistant organisms by broad-spectrum antimicrobial agents. This study investigated the clinical efficacy of 3GC therapy for Enterobacter spp. and Klebsiella aerogenes bacteremia in a multicenter, retrospective, observational study. Methods Patients with Enterobacter spp. or Klebsiella aerogenes detected in blood cultures and treated with a susceptible antimicrobial agent were included in the study. Propensity score matching was performed to align patient background bases, and clinical outcomes between the 3GC and non-3GC groups were compared. Treatment success was defined as having no need for treatment escalation or the addition of other antimicrobial agents, no recurrence, or no death within 30 days. Results The study included 188 cases, of which 57 and 131 were included in the 3GC and non-3GC treatment groups, respectively; 53 patients in each group were matched by propensity score matching. There were no significant differences between groups in rates of switching to a susceptible antimicrobial or adding another agent, relapse within 30 days, or death within 30 days. In the 3GC group, source control was associated with favorable clinical outcomes. Conclusion Definitive 3GC therapy for susceptible Enterobacter spp. and Klebsiella aerogenes bacteremia is as clinically effective and valuable a targeted therapy as non-3GC therapy and can be implemented under conditions in which infection source control measures are in place.

Purulent Pericarditis Due to Pneumococcal Bacteremia Caused by Acupuncture: An Autopsy Case Report.

Purulent pericarditis is an infection of the pericardial cavity that produces purulent fluid and is commonly caused by Streptococcus pneumoniae. We herein report an autopsy case that is unique in two respects: the patient had pneumococcal bacteremia from a skin and soft tissue infection associated with acupuncture as well as purulent pericarditis from pneumococcal bacteremia. This case suggests that bloodstream infection should be included in the differential diagnosis on observing pneumococcal pericarditis. Furthermore, it is necessary to recognize that S. pneumoniae may be the organism responsible for skin and soft tissue infections caused by trauma in immunosuppressed patients.

Clinical characteristics and treatment of IMP-type carbapenemase-producing Enterobacteriaceae bacteremia: Case series and literature review.

BACKGROUND: Several carbapenemases have been identified globally in Enterobacteriaceae. In Japan, IMP-type carbapenemase is the most prevalent, although cases of carbapenemase-producing Enterobacteriaceae (CPE) bacteremia are still scarce. The present case series and literature review aimed to elucidate the clinical characteristics and treatment strategies for IMP-type CPE bacteremia. METHODS: Clinical data on pediatric cases of IMP-type CPE bacteremia at the Tokyo Metropolitan Children's Medical Center between 2010 and 2020 were collected, and a review of past studies of IMP-type CPE bacteremia has been provided. RESULTS: Five pediatric episodes of IMP-type CPE bacteremia were identified. Our review of previous literature on IMP-type CPE bacteremia revealed 24 adult patients, but no pediatric patients. All 29 cases had underlying diseases, and 23 (79%) received combination therapy. The median duration of antibiotic therapy was 14 days (interquartile range: 9-14 days). The overall mortality rate was 38% (11/29). The mortality rates associated with monotherapy and combination therapy were 67% (4/6) and 30% (7/23), respectively. CONCLUSIONS: We report the first case series of IMP-type CPE bacteremia in children. Our review of past studies suggests that combination therapy might lead to better survival outcomes in patients with IMP-type CPE bacteremia. Further research is needed to establish an optimal treatment strategy for IMP-type CPE bacteremia.