Tocilizumab for the treatment of adult patients with severe COVID-19 pneumonia: A single-center cohort study.

Coronavirus disease 2019 (COVID-19) can lead to a massive cytokine release. The use of the anti-interleukin-6 receptor monoclonal antibody tocilizumab (TCZ) has been proposed in this hyperinflammatory phase, although supporting evidence is limited. We retrospectively analyzed 88 consecutive patients with COVID-19 pneumonia that received at least one dose of intravenous TCZ in our institution between 16 and 27 March 2020. Clinical status from day 0 (first TCZ dose) through day 14 was assessed by a 6-point ordinal scale. The primary outcome was clinical improvement (hospital discharge and/or a decrease of ≥2 points on the 6-point scale) by day 7. Secondary outcomes included clinical improvement by day 14 and dynamics of vital signs and laboratory values. Rates of clinical improvement by days 7 and 14 were 44.3% (39/88) and 73.9% (65/88). Previous or concomitant receipt of subcutaneous interferon-ß (adjusted odds ratio [aOR]: 0.23; 95% confidence interval [CI]: 0.06-0.94; P = .041) and serum lactate dehydrogenase more than 450 U/L at day 0 (aOR: 0.25; 95% CI: 0.06-0.99; P = .048) were negatively associated with clinical improvement by day 7. All-cause mortality was 6.8% (6/88). Body temperature and respiratory and cardiac rates significantly decreased by day 1 compared to day 0. Lymphocyte count and pulse oximetry oxygen saturation/FiO2 ratio increased by days 3 and 5, whereas C-reactive protein levels dropped by day 2. There were no TCZ-attributable adverse events. In this observational single-center study, TCZ appeared to be useful and safe as immunomodulatory therapy for severe COVID-19 pneumonia.

Impact of viral load at admission on the development of respiratory failure in hospitalized patients with SARS-CoV-2 infection.

The aim of our study was to elucidate if SARS-CoV-2 viral load on admission, measured by real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) cycle threshold (Ct) value on nasopharyngeal samples, was a marker of disease severity. All hospitalized adult patients with a diagnosis of SARS-CoV-2 infection by rRT-PCR performed on a nasopharingeal sample from March 1 to March 18 in our institution were included. The study population was divided according to the Ct value obtained upon admission in patients with high viral load (Ct < 25), intermediate viral load (Ct: 25-30) and low viral load (Ct > 30). Demographic, clinical and laboratory variables of the different groups were analyzed to assess the influence of viral load on the development of respiratory failure during admission. Overall, 455 sequential patients were included. The median Ct value was 28 (IQR: 24-32). One hundred and thirty patients (28.6%) had a high viral load, 175 (38.5%) an intermediate viral load and 150 (33%) a low viral load. Advanced age, male sex, presence of cardiovascular disease and laboratory markers such as lactate dehydrogenase, lymphocyte count and C-reactive protein, as well as a high viral load on admission, were predictive of respiratory failure. A Ct value < 25 was associated with a higher risk of respiratory failure during admission (OR: 2.99, 95%IC: 1.57-5.69). SARS-CoV-2 viral load, measured through the Ct value on admission, is a valuable tool to predict the development of respiratory failure in COVID-19 inpatients.

Impact of De-escalation on Prognosis of Patients With Bacteremia due to Enterobacteriaceae: A Post Hoc Analysis From a Multicenter Prospective Cohort.

BACKGROUND: More data are needed about the safety of antibiotic de-escalation in specific clinical situations as a strategy to reduce exposure to broad-spectrum antibiotics. The aims of this study were to investigate predictors of de-escalation and its impact on the outcome of patients with bloodstream infection due to Enterobacteriaceae (BSI-E). METHODS: A post hoc analysis was performed on a prospective, multicenter cohort of patients with BSI-E initially treated with ertapenem or antipseudomonal ß-lactams. Logistic regression was used to analyze factors associated with early de-escalation (EDE) and Cox regression for the impact of EDE and late de-escalation (LDE) on 30-day all-cause mortality. A propensity score (PS) for EDE vs no de-escalation (NDE) was calculated. Failure at end of treatment and length of hospital stay were also analyzed. RESULTS: Overall, 516 patients were included. EDE was performed in 241 patients (46%), LDE in 95 (18%), and NDE in 180 (35%). Variables independently associated with a lower probability of EDE were multidrug-resistant isolates (odds ratio [OR], 0.50 [95% confidence interval {CI}, .30-.83]) and nosocomial infection empirically treated with imipenem or meropenem (OR, 0.35 [95% CI, .14-.87]). After controlling for confounders, EDE was not associated with increased risk of mortality; hazard ratios (HR) (95% CIs) were as follows: general model, 0.58 (.25-1.31); model with PS, 0.69 (.29-1.65); and PS-based matched pairs, 0.98 (.76-1.26). LDE was not associated with mortality. De-escalation was not associated with clinical failure or length of hospital stay. CONCLUSIONS: De-escalation in patients with monomicrobial bacteremia due to Enterobacteriaceae was not associated with a detrimental impact on clinical outcome.

Influence of empirical double-active combination antimicrobial therapy compared with active monotherapy on mortality in patients with septic shock: a propensity score-adjusted and matched analysis.

OBJECTIVES: To evaluate the influence on mortality of empirical double-active combination antimicrobial therapy (DACT) compared with active monotherapy (AM) in septic shock patients. METHODS: A retrospective study was performed of monomicrobial septic shock patients admitted to a university centre during 2010-15. A propensity score (PS) was calculated using a logistic regression model taking the assigned therapy as the dependent variable, and used as a covariate in multivariate analysis predicting 7, 15 and 30 day mortality and for matching patients who received DACT or AM. Multivariate models comprising the assigned therapy group and the PS were built for specific patient subgroups. RESULTS: Five-hundred and seventy-six patients with monomicrobial septic shock who received active empirical antimicrobial therapy were included. Of these, 340 received AM and 236 DACT. No difference in 7, 15 and 30 day all-cause mortality was found between groups either in the PS-adjusted multivariate logistic regression analysis or in the PS-matched cohorts. However, in patients with neutropenia, DACT was independently associated with a better outcome at 15 (OR 0.29, 95% CI 0.09-0.92) and 30 (OR 0.25, 95% CI 0.08-0.79) days, while in patients with Pseudomonas aeruginosa infection DACT was associated with lower 7 (OR 0.12, 95% CI 0.02-0.7) and 30 day (OR 0.26, 95% CI 0.08-0.92) mortality. CONCLUSIONS: All-cause mortality at 7, 15 and 30 days was similar in patients with monomicrobial septic shock receiving empirical double-active combination therapy and active monotherapy. However, a beneficial influence of empirical double-active combination on mortality in patients with neutropenia and those with P. aeruginosa infection is worthy of further study.

A propensity score analysis shows that empirical treatment with linezolid does not increase the thirty-day mortality rate in patients with Gram-negative bacteremia.

The role of linezolid in empirical therapy of suspected bacteremia remains unclear. The aim of this study was to evaluate the influence of empirical use of linezolid or glycopeptides in addition to other antibiotics on the 30-day mortality rates in patients with Gram-negative bacteremia. For this purpose, 1,126 patients with Gram-negative bacteremia in the Hospital Clinic of Barcelona from 2000 to 2012 were included in this study. In order to compare the mortality rates between patients who received linezolid or glycopeptides, the propensity scores on baseline variables were used to balance the treatment groups, and both propensity score matching and propensity-adjusted logistic regression were used to compare the 30-day mortality rates between the groups. The overall 30-day mortality rate was 16.0% during the study period. Sixty-eight patients received empirical treatment with linezolid, and 1,058 received glycopeptides. The propensity score matching included 64 patients in each treatment group. After matching, the mortality rates were 14.1% (9/64) in patients who received glycopeptides and 21.9% (14/64) in those who received linezolid, and a nonsignificant association between empirical linezolid treatment and mortality rate (odds ratio [OR], 1.63; 95% confidence interval [CI], 0.69 to 3.82; P = 0.275, McNemar's test) was found. This association remained nonsignificant when variables that remained unbalanced after matching were included in a conditional logistic regression model. Further, the stratified propensity score analysis did not show any significant relationship between empirical linezolid treatment and the mortality rate after adjustment by propensity score quintiles or other variables potentially associated with mortality. In conclusion, the propensity score analysis showed that empirical treatment with linezolid compared with that with glycopeptides was not associated with 30-day mortality rates in patients with Gram-negative bacteremia.

Time to positivity and detection of growth in anaerobic blood culture vials predict the presence of Candida glabrata in candidemia: a two-center European cohort study.

This study shows the accuracy of exclusive or earlier growth in anaerobic vials to predict Candida glabrata in a large series of candidemic patients from two European hospitals using the Bactec 9240 system. Alternatively, C. glabrata can be predicted by a time to positivity cutoff value, which should be determined for each setting.

Impact of a Hospitalist Co-Management Program on Medical Complications and Length of Stay in Neurosurgical Patients.

BACKGROUND: The impact of co-management on clinical outcomes in neurosurgical patients is uncertain. This study aims to describe the implementation of a hospitalist co-management program in a neurosurgery department and its impact on the incidence of complications, mortality, and length of stay. METHODS: The authors used a quasi-experimental study design that compared a historical control period (July-December 2017) to a prospective intervention arm. During the intervention period, patients admitted to a neurosurgery inpatient unit who were older than 65 years, suffered certain conditions, or were admitted from ICUs were included in the co-management program. Two hospitalists joined the surgical staff and intervened in the diagnostic and therapeutical plan of patients, participating in clinical decisions and coordinating patient navigation with neurosurgeons. The incidence of moderate or severe complications measured by the Accordion Severity Grading System, in-hospital mortality, and length of stay of the two cohorts were compared. Multivariate regression was used to adjust for confounders, and the average treatment effect was estimated using inverse probability of treatment weighting. RESULTS: The adjusted incidence of moderate or severe complications was lower among co-managed patients (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.39-0.91). Mortality was unchanged (OR 0.83, 95% CI 0.15-4.17). Length of stay was lower in co-managed patients, with a 1.3-day reduction observed after inverse probability of treatment weighting analysis. CONCLUSION: Hospitalist co-management was associated with a reduced incidence of complications and length of stay in neurosurgical patients, but there was no difference in in-hospital mortality.

Usefulness of time-to-positivity in aerobic and anaerobic vials to predict the presence of Candida glabrata in patients with candidaemia.

OBJECTIVES: To determine whether time-to-positivity (TTP) in aerobic and anaerobic blood culture vials is useful to predict the presence of Candida glabrata in patients with candidaemia. METHODS: TTP was recorded for both aerobic and anaerobic vials for each blood culture set of monomicrobial candidaemia. We considered TTP as the shortest time registered for any positive vial. Two diagnostic criteria were evaluated: the cut-off TTP value as obtained from a receiver operating characteristic curve and the detection of growth only or with a shorter TTP in anaerobic vials. RESULTS: A total of 157 episodes were analysed of which 19 (12.1%) were due to C. glabrata. The TTP for C. glabrata was longer than that for other species. C. glabrata grew more frequently than other species in anaerobic vials [9/19 (47%) versus 19/138 (14%); P = 0.001] and also more often exclusively or earlier in anaerobic vials [7/19 (37%) versus 5/138 (4%); P < 0.0001]. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of a TTP >56.5 h for predicting the presence of C. glabrata were 47%, 88%, 36% and 92%, respectively. Growth detection only or earlier in anaerobic flasks had a sensitivity of 37%, a specificity of 96%, a PPV of 58% and an NPV of 92%. CONCLUSIONS: Using the BACTEC 9240 system, a TTP ≤ 56.5 h is useful to rule out C. glabrata. In addition, in settings with an ~12% prevalence of C. glabrata candidaemia, yeast detection exclusively or earlier in anaerobic vials increases the probability of the presence of C. glabrata to 58%, which may be useful for early treatment optimization.

Cannabinoid receptor 1 gene is associated with alcohol dependence.

BACKGROUND: Alcohol dependence (AD) vulnerability is determined by a complex array of genetic factors. Given the potential role of endocannabinoid system in AD, polymorphisms within cannabinoid receptor 1 gene (CNR1) have been potentially associated with susceptibility to this disease. We thus aimed to examine the relationship between 3 allelic variants of CNR1 (rs6454674, rs1049353, and rs806368) and AD. METHODS: Genotyping of the aforementioned polymorphisms was carried out by PCR in 298 male alcoholics (187 of them with AD) and 155 healthy controls. Single-marker, haplotype, and interaction analysis were performed to analyze the influence of CNR1 gene on AD susceptibility. RESULTS: We found an association between CNR1 gene and AD after haplotype analysis. Alcoholic patients with TGT haplotype (corresponding to rs6454674-rs1049353-rs806368 polymorphisms in this order) were less prone to have AD (p = 0.017). Besides, alcoholics with a G/T substitution of the first marker (GGT haplotype) or a C/T substitution of the third marker (TGC haplotype) were more likely to develop AD (p = 0.006 and 0.004, respectively) and an interaction was found between the G allele of rs6454674 single nucleotide polymorphism (SNP) and the C allele of rs806368 SNP (p = 0.009). CONCLUSIONS: Our findings support previously reported associations of CNR1 with dependence to alcohol and other substances and emphasizes the relevance of endocannabinoid system in AD.

Nitridation effect on lithium iron phosphate cathode for rechargeable batteries.

A novel oxynitride Li0.94FePO3.84N0.16 with olivine structure (space group Pnma, no. 62) has been synthesized by heating a parent LiFePO4 precursor obtained by citrate chemistry in flowing ammonia at 650 °C. The polycrystalline sample has been characterized by X-ray and neutron powder diffraction (NPD), elemental and thermal analysis, scanning electron microscopy (SEM) and electrochemical measurements. Based on the existing contrast between the scattering lengths of the N and O species, a Rietveld refinement of the structure from NPD data revealed that N preferentially occupies the O2 positions, as likely required to fulfil the bonding power of N ions. The refined crystallographic formula implies an oxidation state of 2.2+ for Fe cations. The differential thermal analysis, in still air, shows a strong exothermic peak at 520-540 °C due to the combustion of C contents, which are embedding the olivine particles, as observed by SEM. The electrochemical measurements suggest a better performance for the nitrided sample relative to the unnitrided LiFePO4 material, as far as capacity and cyclability are concerned. A bond-valence energy landscape study reveals a decrease in the percolation activation energy of about 6% upon nitridation, concomitant with the better electrochemical properties of the oxynitride compound. Additionally, ceramic samples prepared under NH3 flow could be obtained as pure and well-crystallized olivine phases at milder temperatures (650 °C) than those usually described in literature.

A predictive score at admission for respiratory failure among hospitalized patients with confirmed 2019 Coronavirus Disease: a simple tool for a complex problem.

Coronavirus Disease 2019 (COVID-19) pandemic has implacably stricken on the wellness of many countries and their health-care systems. The aim of the present study is to analyze the clinical characteristics of the initial wave of patients with COVID-19 attended in our center, and to identify the key variables predicting the development of respiratory failure. Prospective design study with concurrent data retrieval from automated medical records of all hospitalized adult patients who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rRT-PCR assay performed on respiratory samples from March 2nd to 18th, 2020. Patients were followed up to May 1st, 2020 or death. Respiratory failure was defined as a PaO2/FiO2 ratio ≤ 200 mm Hg or the need for mechanical ventilation (either non-invasive positive pressure ventilation or invasive mechanical ventilation). We included 521 patients of whom 416 (81%) had abnormal Chest X-ray on admission. Median age was 64.6 ± 18.2 years. One hundred eighty-one (34.7%) developed respiratory failure after a median time from onset of symptoms of 9 days (IQR 6-11). In-hospital mortality was 23.8% (124/521). The modeling process concluded into a logistic regression multivariable analysis and a predictive score at admission. Age, peripheral pulse oximetry, lymphocyte count, lactate dehydrogenase and C-reactive protein were the selected variables. The model has a good discriminative capacity with an area under the ROC curve of 0.85 (0.82-0.88). The application of a simple and reliable score at admission seems to be a useful tool to predict respiratory failure in hospitalized COVID-19 patients.

Analysis of the factors predicting clinical response to tocilizumab therapy in patients with severe COVID-19.

BACKGROUND: Controversy remains about the efficacy of tocilizumab (TCZ) for the treatment of severe COVID-19. We aimed to analyze the profile of TCZ-respondent patients. METHODS: We retrospectively analyzed a cohort of patients with severe COVID-19 who received off-label TCZ after recommendation by a local committee and were admitted to the University Hospital "12 de Octubre" until May 2020. The primary end point was a significant clinical improvement (SCI) on day 14 after administration of TCZ. Factors independently related to SCI were analyzed by multivariate logistic regression models. RESULTS: Of 428 (63.3%) patients treated with TCZ, 271 (63.3%) experienced SCI. After adjustment for factors related to unfavorable outcomes, TCZ administration within the first 48 hours from admission (odds ratio [OR]: 1.98, 95% confidence Interval [95% CI]: 1.1-3.55; P = 0.02) and ALT levels >100 UI/L at day 0 (OR: 3.28; 95% CI: 1.3-8.1; P = 0.01) were independently related to SCI. The rate of SCI significantly decreased according to the time of TCZ administration: 70.2% in the first 48 hours from admission, 58.5% on days 3-7, and 45.1% after day 7 (P = 0.03 and P = 0.001, respectively). CONCLUSION: TCZ improves the prognosis of patients with COVID-19 the most if treatment starts within the first 48 hours after admission.

Effectiveness of anakinra for tocilizumab-refractory severe COVID-19: A single-centre retrospective comparative study.

OBJECTIVES: A subgroup of patients with SARS-CoV-2 infection was thought to have developed cytokine release syndrome and were treated with tocilizumab; however, a significant percentage of patients evolved. This study aimed to determine the usefulness of anakinra as a rescue treatment for patients with tocilizumab-refractory COVID-19 disease. METHODS: A prospective cohort of patients with COVID-19 pneumonia who received anakinra as salvage therapy after failure of tocilizumab were compared (1:1) with selected controls in a historical cohort of patients treated with tocilizumab. Cases and controls were matched by age, comorbidities, pulse oximetry oxygen saturation to fraction of inspired oxygen (SpO2/FiO2) ratio at baseline, and time elapsed since the initiation of treatment with tocilizumab. The primary outcome was the improvement in clinical status measured by a 6-point ordinal scale, from baseline to day 21. RESULTS: The study included 20 cases and 20 controls (mean age 65.3 ± 12.8 years, 65% males). No differences were found in the clinical improvement rates at 7, 14 and 21 days of follow-up. The in-hospital mortality rate for patients receiving anakinra was 55% vs. 45% in the control group (P = 0.527). CONCLUSIONS: Treatment with anakinra was not useful in improving the prognosis of patients with tocilizumab-refractory severe COVID-19.

Combination therapy with tocilizumab and corticosteroids for aged patients with severe COVID-19 pneumonia: A single-center retrospective study.

BACKGROUND: The role of combination immunomodulatory therapy with systemic corticosteroids and tocilizumab (TCZ) for aged patients with COVID-19-associated cytokine release syndrome remains unclear. METHODS: A retrospective single-center study was conducted on consecutive patients aged ≥65 years who developed severe COVID-19 between 03 March and 01 May 2020 and were treated with corticosteroids at various doses (methylprednisolone 0.5mg/kg/12h to 250mg/24h), either alone (CS group) or associated with intravenous tocilizumab (400-600mg, one to three doses) (CS-TCZ group). The primary outcome was all-cause mortality by day +14, whereas secondary outcomes included mortality by day +28 and clinical improvement (discharge and/or a ≥2 point decrease on a 6-point ordinal scale) by day +14. Propensity score (PS)-based adjustment and inverse probability of treatment weights (IPTW) were applied. RESULTS: Totals of 181 and 80 patients were included in the CS and CS-TCZ groups, respectively. All-cause 14-day mortality was lower in the CS-TCZ group, both in the PS-adjusted (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.17-0.68; P=0.002) and IPTW-weighted models (odds ratio [OR]: 0.38; 95% CI: 0.21-0.68; P=0.001). This protective effect was also observed for 28-day mortality (PS-adjusted HR: 0.38; 95% CI: 0.21-0.72; P=0.003). Clinical improvement by day +14 was higher in the CS-TCZ group with IPTW analysis only (OR: 2.26; 95% CI: 1.49-3.41; P<0.001). The occurrence of secondary infection was similar between both groups. CONCLUSIONS: The combination of corticosteroids and TCZ was associated with better outcomes among patients aged ≥65 years with severe COVID-19.

Impact of Cefotaxime Non-susceptibility on the Clinical Outcomes of Bacteremic Pneumococcal Pneumonia.

BACKGROUND: We aimed to analyze the impact of cefotaxime non-susceptibility on the 30-day mortality rate in patients receiving a third-generation cephalosporin for pneumococcal bacteremic pneumonia. METHODS: We conducted a retrospective observational study of prospectively collected data from the Hospital Clinic of Barcelona. All adult patients with monomicrobial bacteremic pneumonia due to Streptococcus pneumoniae and treated with a third-generation cephalosporin from January 1991 to December 2016 were included. Risk factors associated with 30-day mortality were evaluated by univariate and multivariate analyses. RESULTS: During the study period, 721 eligible episodes were identified, and data on the susceptibility to cefotaxime was obtainable for 690 episodes. Sixty six (10%) cases were due to a cefotaxime non-susceptible strain with a 30-day mortality rate of 8%. Variables associated with 30-day mortality were age, chronic liver disease, septic shock, and the McCabe score. Infection by a cefotaxime non-susceptible S. pneumoniae did not increase the mortality rate. CONCLUSION: Despite the prevalence of cefotaxime, non-susceptible S. pneumoniae has increased in recent years. We found no evidence to suggest that patients hospitalized with bacteremic pneumonia due to these strains had worse clinical outcomes than patients with susceptible strains.

Clinical characteristics and prognosis of infections caused by OXA-48 carbapenemase-producing Enterobacteriaceae in patients treated with ceftazidime-avibactam.

BACKGROUND: Ceftazidime-avibactam has in vitro activity against Gram-negative bacilli that produce Class A, C and some D ß-lactamases, and has been successfully used in the treatment of infections caused by cephalosporin and carbapenem-resistant Enterobacteriaceae. However, actual experience in the treatment of OXA-48 carbapenemase-producing Enterobacteriaceae (CPE) is limited. OBJECTIVE: To review the characteristics and prognosis of OXA-48 CPE infections treated with ceftazidime-avibactam since introduction of the drug to the current centre during the period October 2014 to December 2016. METHODS: Retrospective assessment of episodes of infection caused by OXA-48 CPE treated with ceftazidime-avibactam, analysing data collected from infection diagnosis until 90 days after the end of treatment. RESULTS: Twenty-four episodes were analysed. Ceftazidime-avibactam was given as the initial definitive treatment in 15 (62.5%) and as salvage therapy in nine (37.5%). Intraabdominal (seven, 29%), urinary (six, 25%) and respiratory (five, 21%) were the most common sources. The 30-day and 90-day mortality rates were 8.3% and 20.8%, respectively. Clinical cure at 30 days was achieved in 62.5% of episodes. Four (16.7%) patients had adverse events, two of them were related to impaired renal function. Among patients who finished the treatment with ceftazidime-avibactam, seven (35%) were diagnosed with infection recurrence within 90 days of the end of treatment. CONCLUSIONS: From experience, ceftazidime-avibactam is an effective drug for treating infections due to OXA-48 CPE. From these results a better safety profile than the current best available therapy could be expected.

Evaluation of ceftazidime/avibactam for serious infections due to multidrug-resistant and extensively drug-resistant Pseudomonas aeruginosa.

OBJECTIVES: The steady progress in resistance of Pseudomonas aeruginosa (PA) has led to difficulties in treating infections due to multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. Ceftazidime/avibactam (CAZ/AVI) has in vitro activity against many of these strains, however clinical experience with CAZ/AVI is limited. This study aimed to evaluate the characteristics and outcomes of eight patients with infections due to MDR- or XDR-PA treated with CAZ/AVI, including four strains resistant to ceftolozane/tazobactam. METHODS: This was a retrospective descriptive study of patients admitted to a teaching hospital between January 2016 and May 2017 who received CAZ/AVI as initial or continuation therapy for infection due to MDR- and XDR-PA. RESULTS: The sources of infection were hospital-acquired lower respiratory tract infection in five patients (62.5%) and osteomyelitis, meningitis and catheter-related bacteraemia in one patient each. Clinical cure was achieved in 4 patients (50.0%). The 30-day and 90-day mortality rates were 12.5% and 37.5%, respectively. One patient (12.5%) developed encephalopathy that improved with discontinuation of the drug. CONCLUSIONS: CAZ/AVI may be a valuable option for serious infections due to resistant PA.

Comparison of Predictors and Mortality Between Bloodstream Infections Caused by ESBL-Producing Escherichia coli and ESBL-Producing Klebsiella pneumoniae.

OBJECTIVETo compare the epidemiology, clinical characteristics, and mortality of patients with bloodstream infections (BSI) caused by extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (ESBL-EC) versus ESBL-producing Klebsiella pneumoniae (ESBL-KP) and to examine the differences in clinical characteristics and outcome between BSIs caused by isolates with CTX-M versus other ESBL genotypesMETHODSAs part of the INCREMENT project, 33 tertiary hospitals in 12 countries retrospectively collected data on adult patients diagnosed with ESBL-EC BSI or ESBL-KP BSI between 2004 and 2013. Risk factors for ESBL-EC versus ESBL-KP BSI and for 30-day mortality were examined by bivariate analysis followed by multivariable logistic regression.RESULTSThe study included 909 patients: 687 with ESBL-EC BSI and 222 with ESBL-KP BSI. ESBL genotype by polymerase chain reaction amplification of 286 isolates was available. ESBL-KP BSI was associated with intensive care unit admission, cardiovascular and neurological comorbidities, length of stay to bacteremia >14 days from admission, and a nonurinary source. Overall, 30-day mortality was significantly higher in patients with ESBL-KP BSI than ESBL-EC BSI (33.7% vs 17.4%; odds ratio, 1.64; P=.016). CTX-M was the most prevalent ESBL subtype identified (218 of 286 polymerase chain reaction-tested isolates, 76%). No differences in clinical characteristics or in mortality between CTX-M and non-CTX-M ESBLs were detected.CONCLUSIONSClinical characteristics and risk of mortality differ significantly between ESBL-EC and ESBL-KP BSI. Therefore, all ESBL-producing Enterobacteriaceae should not be considered a homogeneous group. No differences in outcomes between genotypes were detected.CLINICAL TRIALS IDENTIFIERClinicalTrials.gov. Identifier: NCT01764490.Infect Control Hosp Epidemiol 2018;39:660-667.

Time to blood culture positivity as a predictor of clinical outcomes and severity in adults with bacteremic pneumococcal pneumonia.

OBJECTIVES: We aimed to investigate the association between the time to positivity of blood culture (TTP) with clinical outcome and severity of pneumococcal bacteremic pneumonia. METHODS: Prospective observational study carried out in 278 hospitalized adult CAP patients with positive blood culture for Streptococcus pneumonia (2003-2015). RESULTS: A total of 278 cases of bacteremic pneumococcal pneumonia were analyzed, median age 62 (46; 79) years. Fifty-one percent of the cases had PSI IV-V. Twenty-one (8%) died within 30-days after admission. The analysis of the TTP showed that the first quartile of the TTP (9.2h) was the best cut-off for differentiating 2 groups of patients at risk, early (TTP <9.2 h) and late (TTP ≥9.2 h) detection groups (AUC 0.66 [95% CI 0.53 to 0.79]). Early TTP was associated with a statistically significant risk of invasive mechanical ventilation (18% vs. 6%, p = 0.007), longer length of hospital stay (12 days vs. 8 days, p<0.001), higher in-hospital mortality (15% vs. 4%, p = 0.010), and 30-day mortality (15% vs. 5%, p = 0.018). After adjustment for potential confounders, regression analyses revealed early TTP as independently associated with high risk of invasive mechanical ventilation (OR 4.60, 95% CI 1.63 to 13.03), longer length of hospital stay (ß 5.20, 95% CI 1.81 to 8.52), higher in-hospital mortality (OR 5.35, 95% CI 1.55 to 18.53), and a trend to higher 30-day mortality (OR 2.47, 95% CI 0.85 to 7.21) to be a contributing factor. CONCLUSION: Our results demonstrate that TTP is an easy to obtain surrogate marker of the severity of pneumococcal pneumonia and a good predictor of its outcome.