This double-blind, multicenter trial compared the efficacy and safety of a single daily oral dose of moxifloxacin with oral combination therapy in low-risk febrile neutropenic patients with cancer.
...Inclusion criteria were cancer, febrile neutropenia, low risk of complications as predicted by a Multinational Association for Supportive Care in Cancer (MASCC) score > 20, ability to swallow, and ≤ one single intravenous dose of empiric antibiotic therapy before study drug treatment initiation. Early discharge was encouraged when a set of predefined criteria was met. Patients received either moxifloxacin (400 mg once daily) monotherapy or oral ciprofloxacin (750 mg twice daily) plus amoxicillin/clavulanic acid (1,000 mg twice daily). The trial was designed to show equivalence of the two drug regimens in terms of therapy success, defined as defervescence and improvement in clinical status during study drug treatment (< 10% difference).
Among the 333 patients evaluated in an intention-to-treat analysis, therapy success was observed in 80% of the patients administered moxifloxacin and in 82% of the patients administered combination therapy (95% CI for the difference, -10% to 8%, consistent with equivalence). Minor differences in tolerability, safety, and reasons for failure were observed. More than 50% of the patients in the two arms were discharged on protocol therapy, with 5% readmissions among those in either arm. Survival was similar (99%) in both arms.
Monotherapy with once daily oral moxifloxacin is efficacious and safe in low-risk febrile neutropenic patients identified with the help of the MASCC scoring system, discharged early, and observed as outpatients.
•The growing problem of antibiotic resistance is a major public health concern.•An antimicrobial stewardship study was conducted in intensive care units.•There was a significant increase in total ...quality-of-care scores.
One of the most important public health concerns is the ever-growing problem of antibiotic resistance. Importantly, the rate of introduction of new molecules into clinical practice has slowed down considerably. Moreover, the rapid emergence of resistance shortens the effective ‘lifespan’ of these molecules.
The quality of care before and after active intervention and feedback was evaluated in patients diagnosed with sepsis/septic shock or ventilator-associated pneumonia (VAP) in the ICUs of Hacettepe University Adult and Oncology Hospitals.
There was a significant increase in total scores. Significant improvements were achieved in the management of these patients in terms of requests for necessary diagnostic tests, and the prolonged infusion of beta-lactam agents.
Implementation of an ASP in centers where antimicrobial management of ICU patients is largely controlled by infectious diseases specialists remains a feasible strategy that leads to better patient care.
Purpose
While more advanced COVID-19 necessitates medical interventions and hospitalization, patients with mild COVID-19 do not require this. Identifying patients at risk of progressing to advanced ...COVID-19 might guide treatment decisions, particularly for better prioritizing patients in need for hospitalization.
Methods
We developed a machine learning-based predictor for deriving a clinical score identifying patients with asymptomatic/mild COVID-19 at risk of progressing to advanced COVID-19. Clinical data from SARS-CoV-2 positive patients from the multicenter Lean European Open Survey on SARS-CoV-2 Infected Patients (LEOSS) were used for discovery (2020-03-16 to 2020-07-14) and validation (data from 2020-07-15 to 2021-02-16).
Results
The LEOSS dataset contains 473 baseline patient parameters measured at the first patient contact. After training the predictor model on a training dataset comprising 1233 patients, 20 of the 473 parameters were selected for the predictor model. From the predictor model, we delineated a composite predictive score (SACOV-19, Score for the prediction of an Advanced stage of COVID-19) with eleven variables. In the validation cohort (
n
= 2264 patients), we observed good prediction performance with an area under the curve (AUC) of 0.73 ± 0.01. Besides temperature, age, body mass index and smoking habit, variables indicating pulmonary involvement (respiration rate, oxygen saturation, dyspnea), inflammation (CRP, LDH, lymphocyte counts), and acute kidney injury at diagnosis were identified. For better interpretability, the predictor was translated into a web interface.
Conclusion
We present a machine learning-based predictor model and a clinical score for identifying patients at risk of developing advanced COVID-19.
Background
Hospital-acquired bloodstream infections are common in the intensive care unit (ICU) and have a high mortality rate. Patients with cirrhosis are especially susceptible to infections, yet ...there is a knowledge gap in the epidemiological distinctions in hospital-acquired bloodstream infections between cirrhotic and non-cirrhotic patients in the ICU. It has been suggested that cirrhotic patients, present a trend towards more gram-positive infections, and especially enterococcal infections. This study aims to describe epidemiological differences in hospital-acquired bloodstream infections between cirrhotic and non-cirrhotic patients hospitalized in the ICU regarding infection sources, microorganisms and mortality.
Methods
Using prospective Eurobact-2 international cohort study data, we compared hospital-acquired bloodstream infections sources and microorganisms in cirrhotic and non-cirrhotic patients. The association between
Enterococcus faecium
and cirrhosis was studied using a multivariable mixed logistic regression. The association between cirrhosis and mortality was assessed by a multivariable frailty Cox model.
Results
Among the 1059 hospital-acquired bloodstream infections patients included from 101 centers, 160 had cirrhosis. Hospital-acquired bloodstream infection source in cirrhotic patients was primarily abdominal (35.6%), while it was pulmonary (18.9%) for non-cirrhotic (
p
< 0.01). Gram-positive hospital-acquired bloodstream infections accounted for 42.3% in cirrhotic patients compared to 33.2% in non-cirrhotic patients (
p
= 0.02). Hospital-acquired bloodstream infections in cirrhotic patients were most frequently caused by
Klebsiella
spp (16.5%), coagulase-negative Staphylococci (13.7%) and
E. faecium
(11.5%).
E. faecium
bacteremia was more frequent in cirrhotic patients (11.5%
versus
4.5%,
p
< 0.01). After adjusting for possible confounding factors, cirrhosis was associated with higher
E. faecium
hospital-acquired bloodstream infections risk (Odds ratio 2.5, 95% CI 1.3–4.5,
p
< 0.01). Cirrhotic patients had increased mortality compared to non-cirrhotic patients (Hazard Ratio 1.3, 95% CI 1.01–1.7,
p
= 0.045).
Conclusions
Critically ill cirrhotic patients with hospital-acquired bloodstream infections exhibit distinct epidemiology, with more Gram-positive infections and particularly
Enterococcus faecium
.
A global cross-sectional survey was performed to gather data on the current treatment of infections caused by multidrug-resistant (MDR) bacteria among hematological patients admitted to ICUs ...worldwide. The survey was performed in April 2019 using an electronic platform (SurveyMonkey®) being distributed among 83 physicians and completed by 48 (57.8%) responders. ESBL Enterobacteriaceae, carbapenem-resistant
K. pneumoniae
and carbapenem-resistant
P. aeruginosa
were the main concerns. Previous MDR infection (34% of responders), MDR colonization (20%) and previous antibiotic exposure within the last 3 months (20.5%) were considered the most relevant risk factors of bloodstream infection (BSI) due to MDR bacteria. In 48.8% of the ICUs, there was no antimicrobial stewardship (AMS) team focused on hematological patients. Updates on local epidemiology of MDR pathogens were provided in 98% of the centers, using phone or verbal communications (56.1% and 53.7%, respectively). In presence of febrile neutropenia, initial therapy consisted of anti-Gram-negative plus anti-Gram-positive antibiotics for 41% of participants. Antibiotic de-escalation and/or discontinuation of therapy were considered as a promising strategy for the prevention of MDR development (32.4%). Factors associated with antibiotic de-escalation were clinical improvement (43.6%) and neutrophil count recovery (12.8%). Infectious Disease consultation and AMS interventions were not determining factors for de-escalation decisions (more than 50% of responders). Infection control and educational programs were valued as necessary measures for implementation by ICU practitioners. These findings should guide future efforts on collaborative team working, improving compliance with adequate treatment protocols, implementing antimicrobial stewardship programs in critically ill hematological patients, and educational activities.
Inequitable vaccine availability adds to the problem as on one hand, in many high-income countries, a fourth dose of an mRNA vaccine is offered and gives well tolerated boosting of cellular and ...humoral immunity,1 and on the other hand, only 19·7% of people in low-income countries have received at least one dose of any COVID-19 vaccine.2 These facts all make it difficult to comment on what a primary COVID-19 vaccination series should consist of and how we should boost protective immunity in the face of emerging variants in a world with marked inequalities. ...the final analysis of the double-blind phase of the ENSEMBLE vaccine trial showed that primary vaccination with a single dose of Ad26.COV2.S had 56·3% (95% CI 51·3–60·8) efficacy against moderate to severe–critical COVID-19, 74·6% (64·7–82·1) efficacy against severe–critical COVID-19, and 82·8% (40·5–96·8) efficacy against COVID-19 related death.4 The data collection for the primary analyses of one-dose and two-dose regimens was completed before the global dominance of delta (B.1.617.2) and the emergence of omicron. ...we consider that two doses should be regarded as the primary vaccination series for Ad26.COV2.S in the era of omicron.
Coronavirus disease 2019 (COVID-19) continues to pose a threat to public health with the potential for the emergence of new variants. Vaccines are the milestones to control and slow down the damage ...of the pandemic. As of January 2021, a two-dose regimen with CoronaVac was authorized in Turkey. Due to the waning seroprevalence rate of SARS-CoV-2 over time, BNT162b2 or CoronaVac has been administered as the third dose following a two-dose CoronaVac regimen as a national vaccination policy. As of 14 January 2021, 5243 volunteers who received two doses of the CoronaVac vaccine at Hacettepe University Adult Vaccine Center were followed prospectively. In our study, relative vaccine effectiveness (VEff) for the third dose of the CoronaVac was 58.24% and 87.27% for BNT162b2 in preventing symptomatic COVID-19 cases. There were no hospitalizations, intensive care unit admissions, or deaths in third-dose booster groups with either BNT162b2 or CoronaVac, yielding 100% effectiveness. Both homologous or heterologous third-dose boosters provided further protection against severe COVID-19 and should be prioritized as an effective strategy to combat the COVID-19 pandemic.
Objectives: 1-(1-Naphthylmethyl)-piperazine (NMP) has been shown to reverse multidrug resistance (MDR) in Escherichia coli overexpressing RND type efflux pumps, but there is no data on its activity ...in Enterobacteriaceae other than E. coli. Methods: The antimicrobial susceptibilities of laboratory strains and 167 clinical isolates of Enterobacteriaceae to a variety of antimicrobial agents were determined in the absence and presence of NMP and, for comparison, of Phe-Arg-β-naphthylamide (PAβN), another putative efflux pump inhibitor (EPI). A 4-fold or greater reduction of the MIC after EPI addition was considered significant. Results: NMP consistently reduced the MIC of linezolid in Citrobacter freundii, Enterobacter aerogenes and Klebsiella pneumoniae clinical isolates. Significant effects of NMP addition in >50% of tested isolates were also seen for levofloxacin, tetracycline and chloramphenicol in E. aerogenes, and for levofloxacin and tetracycline in K. pneumoniae, whereas no or minor effects were observed in Serratia marcescens. MDR reversal by NMP was more likely in isolates with decreased susceptibility to fluoroquinolones. In most fluoroquinolone-resistant strains the activity was sufficient to render isolates drug-susceptible at clinically achievable concentrations. The activity of PAβN was different from that of NMP, suggesting different modes of action of the two putative EPIs. Conclusion: NMP has moderate activity in reversing MDR in many but not all members of the Enterobacteriaceae family including clinical isolates. Its effects on resistance reversal depend on bacterial species and drug, and are different from those seen with PAβN.
Objectives: To assess the clinical features and outcomes of Pseudomonas aeruginosa bloodstream infection (PA BSI) in neutropenic patients with hematological malignancies (HM) and with solid tumors ...(ST), and identify the risk factors for 30-day mortality. Methods: We performed a large multicenter, retrospective cohort study including onco-hematological neutropenic patients with PA BSI conducted across 34 centers in 12 countries (January 2006−May 2018). Episodes occurring in hematologic patients were compared to those developing in patients with ST. Risk factors associated with 30-day mortality were investigated in both groups. Results: Of 1217 episodes of PA BSI, 917 occurred in patients with HM and 300 in patients with ST. Hematological patients had more commonly profound neutropenia (0.1 × 109 cells/mm) (67% vs. 44.6%; p < 0.001), and a high risk Multinational Association for Supportive Care in Cancer (MASCC) index score (32.2% vs. 26.7%; p = 0.05). Catheter-infection (10.7% vs. 4.7%; p = 0.001), mucositis (2.4% vs. 0.7%; p = 0.042), and perianal infection (3.6% vs. 0.3%; p = 0.001) predominated as BSI sources in the hematological patients, whereas pneumonia (22.9% vs. 33.7%; p < 0.001) and other abdominal sites (2.8% vs. 6.3%; p = 0.006) were more common in patients with ST. Hematological patients had more frequent BSI due to multidrug-resistant P. aeruginosa (MDRPA) (23.2% vs. 7.7%; p < 0.001), and were more likely to receive inadequate initial antibiotic therapy (IEAT) (20.1% vs. 12%; p < 0.001). Patients with ST presented more frequently with septic shock (45.8% vs. 30%; p < 0.001), and presented worse outcomes, with increased 7-day (38% vs. 24.2%; p < 0.001) and 30-day (49% vs. 37.3%; p < 0.001) case-fatality rates. Risk factors for 30-day mortality in hematologic patients were high risk MASCC index score, IEAT, pneumonia, infection due to MDRPA, and septic shock. Risk factors for 30-day mortality in patients with ST were high risk MASCC index score, IEAT, persistent BSI, and septic shock. Therapy with granulocyte colony-stimulating factor was associated with survival in both groups. Conclusions: The clinical features and outcomes of PA BSI in neutropenic cancer patients showed some differences depending on the underlying malignancy. Considering these differences and the risk factors for mortality may be useful to optimize their therapeutic management. Among the risk factors associated with overall mortality, IEAT and the administration of granulocyte colony-stimulating factor were the only modifiable variables.
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