scholarly journals 2293. Revival of Polymyxins: A Single-Center Historical Cohort of Critically Ill Patients in Brazil

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S786-S786
Author(s):  
Claudia Maria Dantas de Maio Carrilho ◽  
Thalita Bento Talizin ◽  
Camila R Lopes ◽  
Isabella Patruceli Azevedo ◽  
Kesia Paes ◽  
...  

Abstract Background The epidemiological scenario of multidrug-resistant bacteria has brought polymyxins back to medical prescriptions, as they are last-line therapy against carbapenem-resistant bacteria. There is a lack of knowledge of which is the best way to use this drug, especially in critically ill patients. We aimed to evaluate polymyxin use in an intensive care unit (ICU) in a university hospital and to describe its epidemiological characteristics. Methods This historical cohort included all consecutive patients who used polymyxins to treat ventilator-associated pneumonia from January 1, 2017 to January 31, 2018, during hospitalization in an ICU from a public university hospital, endemic for carbapenem-resistant bacteria, in Londrina, Brazil. Microbiological processing for diagnosis followed the guidelines from the Clinical and Laboratory Standards Institute (CLSI). Statistical analyses were performed using MedCalc for Windows, version 18.9 (MedCalc Software, Ostend, Belgium) and significance level adopted was 0.05. Results There were 179 patients; median of age was 57 years (IQR: 40.0 - 70.75). Polymyxin B was the most prescribed polymyxin (97.2%). Most of the patients had comorbidities (72.6%). Age was higher in the group of patients who died (60.0 vs. 36.5 years, P < 0.0001). Comorbidities prevalence was higher in non-survivors (80.7% vs. 38.2%, P < 0.0001). Sequential Organ Failure Assessment (SOFA) score on polymyxin prescribing day was higher in non-survivors (8.0 vs. 7.0, P = 0.0093), as well as Simplified Acute Physiology Score 3 (SAPS 3) score (70.7 vs. 59.35, P = 0.0003). Thirty-day mortality was 43%. Analysis of 14-day survival showed a higher mortality for patients who had sepsis (Log-rank test, P = 0.0284) and septic shock (Log-rank test, P = 0.0065). Acinetobacter baumannii was the most common etiologic agent, in 125 samples (73.9%), with 97.6% of resistance to carbapenem and 5.6% of resistance to polymyxins. Conclusion Polymyxin B was the most prescribed polymyxin. Age was higher in non-survivors, as well as comorbidities prevalence, SOFA and SAPS 3 scores. Patients with sepsis and septic shock showed a 14-day higher mortality. Acinetobacter baumannii was the most isolated agent. Carbapenem resistance was high. Disclosures All authors: No reported disclosures.

2021 ◽  
Author(s):  
Yuzhen Qiu ◽  
Wen Xu ◽  
Yunqi Dai ◽  
Ruoming Tan ◽  
Jialin Liu ◽  
...  

Abstract Background: Carbapenem-resistant Klebsiella pneumoniae bloodstream infections (CRKP-BSIs) are associated with high morbidity and mortality rates, especially in critically ill patients. Comprehensive mortality risk analyses and therapeutic assessment in real-world practice are beneficial to guide individual treatment.Methods: We retrospectively analyzed 87 patients with CRKP-BSIs (between July 2016 and June 2020) to identify the independent risk factors for 28-day all-cause mortality. The therapeutic efficacies of tigecycline-and polymyxin B-based therapies were analyzed.Results: The 28-day all-cause mortality and in-hospital mortality rates were 52.87% and 67.82%, respectively, arising predominantly from intra-abdominal (56.32%) and respiratory tract infections (21.84%). A multivariate analysis showed that 28-day all-cause mortality was independently associated with the patient’s APACHE II score (p = 0.002) and presence of septic shock at BSI onset (p = 0.006). All-cause mortality was not significantly different between patients receiving tigecycline- or polymyxin B-based therapy (55.81% vs. 53.85%, p = 0.873), and between subgroups mortality rates were also similar. Conclusions: Critical illness indicators (APACHE II scores and presence of septic shock at BSI onset) were independent risk factors for 28-day all-cause mortality. There was no significant difference between tigecycline- and polymyxin B-based therapy outcomes. Prompt and appropriate infection control should be implemented to prevent CRKP infections.


2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 82-82
Author(s):  
John Theodorus Plukker ◽  
Justin Smit ◽  
Sahin Guler ◽  
Jannet Beukema ◽  
Veronique E. Mul ◽  
...  

82 Background: Neoadjuvant chemoradiotherapy (CRT) is currently considered standard treatment in esophageal cancer patients who are eligible for surgical resection with curative intent. Objective was to evaluate the recurrence pattern after neoadjuvant CRT in patients with esophageal cancer. Methods: We analyzed the results and recurrence patterns from a single center (N=152) in a propensity score matched study between patients treated with neoadjuvant CRT (N=44) and surgery alone (44 from the 108),in the period 2002-2010. Patients treated with neoadjuvant (CROSS schedule) carboplatin/paclitaxel and 41.4 Gy radiotherapy, were compared with a historical cohort of patients with curative intended surgery alone. Surgery was performed through a transthoracic approach with 2-field lymphadenectomy. Results: After matching, the baseline characteristics were equally distributed between both groups (table 1). The response to CRT was 63%, with a pathological complete response of 26%. After a median follow-up of 23 months (7-74 months), lung was the most common site of distant recurrence (16%, N=7), followed by distant lymph nodes (11%, N=5) in the neoadjuvant CRT group, whereas skeletal metastases were the most common site of distant recurrence (18%, N=8), followed by skin or soft tissue (16%, N=7) in the surgical alone group. The estimated 3 and 5 year overall survival was 62% and 55% in the neoadjuvant CRT group, compared to 37% and 31% in the surgery group (Log-rank test: P=0.018). The estimated locoregional free recurrence survival (LRFS) after 3 and 5 years was 79% and 68% in the neoadjuvant CRT group, compared to 44% and 40% in the surgery alone group (Log-rank test: P=0.049). The estimated distant recurrence free survival (DRFS) was 63% and 54% after 3 and 5 years in the neoadjuvant CRT group, compared to 50% and 35% in the surgery alone group (Log-rank test: P=0.314). Conclusions: This neoadjuvant CRT regimen significantly improved oncological outcome compared to surgery alone. An important shift in recurrence pattern was observed from relatively high locoregional recurrences (LRFS) to relatively more distant recurrences (DRFS) in the CRT group compared to the surgery alone group.


2017 ◽  
Vol 34 (1) ◽  
pp. 48-54 ◽  
Author(s):  
Stefano Busani ◽  
Giulia Serafini ◽  
Elena Mantovani ◽  
Claudia Venturelli ◽  
Maddalena Giannella ◽  
...  

Background: Patients with septic shock by multidrug resistant (MDR) microorganism maybe considered a specific population of critical patients at very high risk of death in whom the effects of standard sepsis treatment has never been assessed. The objective of this retrospective analysis was to evaluate the risk factors for 30-day mortality and the impact of sepsis management in patients with septic shock caused by MDR bacteria. Methods: Patients with septic shock by MDR bacteria admitted to the mixed intensive care unit (ICU) of Modena University Hospital during a 6-year period were studied. The clinical and microbiological characteristics and sepsis treatments provided were analyzed and compared between survivors (S) and nonsurvivors (NS) at 30 days after septic shock appearance. Results: Ninety-four patients were studied. All therapeutic interventions applied to patients during their ICU stay did not show statistical significance between S and NS groups, except for administration of immunoglobulin M (IgM) preparation which were provided more frequently in S group ( P < .05). At the multivariate adjusted analysis, preexisting cancer (odds ratio [OR] = 2.965) and Acinetobacter baumannii infections (OR = 3.197) were independently correlated with an increased risk of 30-day mortality, whereas treatment with IgM preparation was protective (OR = 0.283). Conclusions: This retrospective study showed that in patients with septic shock caused by MDR bacteria, history of cancer and infection sustained by A baumannii increase the risk of mortality and that standard sepsis treatments do not seem to provide any protective effect. Adjunctive therapy with IgM preparation seems to be beneficial, but further appropriate studies are needed to confirm the results observed.


2020 ◽  
Author(s):  
Viveka Björck ◽  
Lisa I Påhlman ◽  
Mikael Bodelsson ◽  
Ann_Cathrine Petersson ◽  
Thomas Kander

Abstract Background Group A streptococci (GAS) are known to cause serious invasive infections but little is known about outcomes when patients with these infections are admitted to intensive care. We wanted to describe critically ill patients with severe sepsis or septic shock due to invasive GAS (iGAS) and compare them with other patients with severe sepsis or septic shock. Methods Adult patients admitted to a general intensive care unit (ICU) in Sweden (2007-2019) were screened for severe sepsis or septic shock according to Sepsis 2 definition. Individuals with iGAS infection were identified. The outcome variables were mortality, days alive and free of vasopressors and invasive mechanical ventilation, maximum acute kidney injury score for creatinine, use of continuous renal replacement therapy and maximum sequential organ failure assessment score during the ICU stay. Age, simplified acute physiology score (SAPS 3) and iGAS were used as independent, explanatory variables in regression analysis. Cox regression was used for survival analyses. Results iGAS was identified in 53 of 1021 (5.2%) patients. Patients with iGAS presented lower median SAPS 3 score (62 [56–72]) vs 71 [61–81]), p < 0.001), had a higher frequency of cardiovascular cause of admission to the ICU (38 [72%] vs 145 [15%], p < 0.001) and had a higher median creatinine score (173 [100–311] vs 133 [86–208] µmol/L, p < 0.019). Of the GAS isolates, 50% were serotyped emm 1/T1 and this group showed signs of more pronounced circulatory and renal failure than patients with non- emm 1/T1, ( p = 0.036 and p = 0.007, respectively). After correction for severity of illness (SAPS 3) and age, iGAS infection was associated with lower mortality risk; 95% confidence interval (CI) of hazard ratio (HR) 0.204–0.746, p < 0.001. Morbidity analyses demonstrated that iGAS patients were more likely to develop renal failure. Conclusion Critically ill patients with iGAS infection had a lower mortality risk but a higher degree of renal failure compared to similarly ill sepsis patients. emm 1/T1 was found to be the most dominant serotype and patients with emm1 /T1 demonstrated more circulatory and renal failure than patients with other serotypes of iGAS.


2020 ◽  
Vol 18 (12) ◽  
pp. 1670-1677
Author(s):  
Amy A. Kirkham ◽  
Karen A. Gelmon ◽  
Cheri L. Van Patten ◽  
Kelcey A. Bland ◽  
Holly Wollmann ◽  
...  

Background: Available preliminary evidence is conflicting on whether exercise can positively influence antineoplastic treatment tolerance and in turn improve survival. Patients and Methods: This study compared chemotherapy treatment tolerance and survival among women receiving adjuvant chemotherapy for early-stage breast cancer who participated in a single-arm trial of supervised aerobic and resistance exercise programming versus a historical cohort that did not receive structured exercise programming. Results: The exercise group (EX; n=73) and control group (CTR; n=85) participants were matched on age and treatment and balanced on medical history, cancer diagnosis, and body mass index. Attendance in the EX group was 64% ± 27% of 3 offered sessions per week. For all chemotherapy agents combined, the relative risk (RR) of a chemotherapy dose reduction (RR, 0.78; 95% CI, 0.54–1.11) or delay (RR, 1.05; 95% CI, 0.62–1.80) did not differ between groups. However, the EX group had reduced relative and absolute risks of a dose reduction in doxorubicin by 60% and 18%, respectively. For all agents combined, there were no differences between groups in risk of anemia, neutropenia, or weight gain. In the EX group, dose reductions due to neutropenia (P=.027), other infections (P=.049), and fatigue (P=.037) were less common, whereas mucositis was more common (P=.023), compared with the CTR group. The EX group had reduced relative and absolute risks of weight gain on the docetaxel + cyclophosphamide regimen by 38% and 30%, respectively. After a median follow-up of 70 months (range, 54–84 months), there was no difference between the EX and CTR groups in disease-free survival events (n=8 [11%] vs n=9 [11%], respectively; log-rank test, P=.78) or overall survival events (n=5 [7%] vs n=6 [7%], respectively; log-rank test, P=.974). Conclusions: Overall, exercise programming during adjuvant chemotherapy does not appear to impact treatment tolerance or survival in women receiving common modern regimens of adjuvant chemotherapy for early-stage breast cancer. However, exercise may provide selective benefits, depending on the treatment regimen received.


2019 ◽  
Vol 98 (4) ◽  
pp. 145-151

Complicated intra-abdominal infections (cIAI) are a substantial cause of morbidity at intensive care units. cIAI are frequently caused by multidrug- resistant strains of Enterobacteriaceae and Pseudomonas aeruginosa. In 592 cIAI patients from the First Department of Surgery, General University Hospital in Prague, we found an alarming increase in resistance of Escherichia coli to amoxicillin/clavulanic acid, piperacillin/tazobactam and third-generation cephalosporins in 2014–2017 (from 28.7% in 2014 to 37.5% in 2017, from 25% to 32% and from 2.3% to 5.6%, respectively). Ceftolozane/tazobactam and ceftazidime/avibactam are novel cephalosporins available for the treatment of cIAI. Ceftolozane/tazobactam is highly active against multidrug-resistant strains of P. aeruginosa, including carbapenem-resistant isolates. The new non-b-lactam b-lactamase inhibitor avibactam plus ceftazidime is active against carbapenemases-producing strains of Enterobacteriaceae. Both antibiotics are included in the new WSES guidelines for the management of cIAI.


2013 ◽  
Vol 57 (11) ◽  
pp. 5394-5397 ◽  
Author(s):  
Yanina Dubrovskaya ◽  
Ting-Yi Chen ◽  
Marco R. Scipione ◽  
Diana Esaian ◽  
Michael S. Phillips ◽  
...  

ABSTRACTPolymyxins are reserved for salvage therapy of infections caused by carbapenem-resistantKlebsiella pneumoniae(CRKP). Though synergy has been demonstrated for the combination of polymyxins with carbapenems or tigecycline,in vitrosynergy tests are nonstandardized, and the clinical effect of synergy remains unclear. This study describes outcomes for patients with CRKP infections who were treated with polymyxin B monotherapy. We retrospectively reviewed the medical records of patients with CRKP infections who received polymyxin B monotherapy from 2007 to 2011. Clinical, microbiology, and antimicrobial treatment data were collected. Risk factors for treatment failure were identified by logistic regression. Forty patients were included in the analysis. Twenty-nine of 40 (73%) patients achieved clinical cure as defined by clinician-documented improvement in signs and symptoms of infections, and 17/32 (53%) patients with follow-up culture data achieved microbiological cure. End-of-treatment mortality was 10%, and 30-day mortality was 28%. In a multivariate analysis, baseline renal insufficiency was associated with a 6.0-fold increase in clinical failure after adjusting for septic shock (odds ratio [OR] = 6.0; 95% confidence interval [CI] = 1.22 to 29.59). Breakthrough infections with organisms intrinsically resistant to polymyxins occurred in 3 patients during the treatment. Eighteen of 40 (45%) patients developed a new CRKP infection a median of 23 days after initial polymyxin B treatment, and 3 of these 18 infections were polymyxin resistant. The clinical cure rate achieved in this retrospective study was 73% of patients with CRKP infections treated with polymyxin B monotherapy. Baseline renal insufficiency was a risk factor for treatment failure after adjusting for septic shock. Breakthrough infections with organisms intrinsically resistant to polymyxin B and development of resistance to polymyxin B in subsequent CRKP isolates are of concern.


BMJ Open ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. e023259 ◽  
Author(s):  
Keisuke Sako ◽  
Kengo Furuichi ◽  
Yuta Yamamura ◽  
Megumi Oshima ◽  
Tadashi Toyama ◽  
...  

ObjectivesRecurrent acute kidney injury (AKI) is a recognised risk factor for mortality. However, it is unclear whether the period until AKI recurrence may have a major factor on patient outcome or not. To explore this issue, we (1) framed the hypothesis that early recurrence increases the risk of mortality and (2) evaluated the prognosis of recurrent AKI cases by setting 21 days as the cut-off period.MethodsAll studied cases were admitted and followed up at the Kanazawa University Hospital (Kanazawa, Japan) between 1 November 2006 and 31 October 2007. In total, 21 939 patients were retrospectively evaluated in their recurrences of AKI for 2 years and followed up until 31 October 2016. Risks for death were evaluated by the recurrences of AKI (Analysis 1). Patients who developed AKI recurrence before 21 days were defined as the early-recurrence group and the remaining cases as the late-recurrence group. Risks for death were evaluated by the two groups (Analysis 2).Results510 patients (2.3%) developed the first AKI. Of these, 151 developed recurrent AKI within 2 years. The number of early-recurrence cases was 44 and that of non-recurrence or late-recurrence was 357. A total of 196 cases (38.4%) died, and higher risk for death was observed in the recurrent AKI group (Analysis 1; p=0.015, log-rank test). We found that the rate of all-cause mortality was higher in the early-recurrence group involving 33.8 deaths per 100 person-years, whereas the non-recurrence or late-recurrence group included only 6.2 deaths per 100 person-years (Analysis 2; p<0.001, log-rank test).ConclusionsPatients experiencing recurrent AKI before 21 days from the first AKI clearly showed a relatively poor prognosis. Evidently, careful follow-up for at least 21 days after AKI would be highly useful to detect a recurrence event, possibly leading to a better prognosis after AKI.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1435.2-1436
Author(s):  
D. Astorri ◽  
F. Ometto ◽  
L. Friso ◽  
B. Raffeiner ◽  
C. Botsios ◽  
...  

Background::In recent years several biosimilars (BS) of tumour necrosis factor inhibitors (TNF-i) were introduced. At the Padova University Hospital the first BS of etanercept (bsETN) was available in October 2016 and the BS of adalimumab (bsADA) was available in November 2018.Objectives:The objectives of the study were to evaluate the rate of bioriginator-biosimilar (BO-BS) switch in all patients with rheumatoid arthritis (RA), psoriatic arthritis (PSA) and axial spondiloarthritis (axSpA) in the cohort of the Padova University Hospital and to examine factors favouring BO-BS switch. Secondly, we investigated survival of BO-BS switch and BO treatment and factors associated with longer treatment survival.Methods:We considered all patients on ETN originator (boETN) treatment when the first bsETN was available (1st October 2016) and all patients on ADA originator (boADA) when bsADA was available (1st November 2018). Patients were followed until 30 August 2019 and were classified as BO-BS switchers if they underwent a switch from either boETN or boADA to BS during the follow-up, otherwise they were considered as continuing BO treatment. Factors associated with BO-BS switch were tested with a multivariable regression analysis. To test the survival of the BO-BS switch and of the BO treatment, Cox regression analysis was used including all variables achiving a p<0.10 in univariate analysis tested with Log-rank test and Kaplan-Meier curves.Results:Among 1208 patients (553 RA, 433 PSA, 215 axSpA), 560 (46.3%) patients switched to bsETN (391) or bsADA (169). Mean disease duration was 16 (14.2) years and mean duration of the bDMARD treatment was 96.3 (56.8) months. After adjustment for potential confounders, factors associated with BO-BS switch were a longer disease duration, a shorter duration of previous bDMARD treatments and diagnosis (Tab.1) RA patients had almost a 3 fold increased likelihood of being switched to BS compared to PSA and axSPA, while difference between PSA and axSPA was not significant.Following Cox regression analysis we observed a longer drug survival in BO-BS switchers compared to those continuing with BO (HR 1.38; 95% C.I. 1.2-1.58; p<0.001) (Fig. 1). A longer drug survival was also associated with a longer disease duration (.15years: HR 1.75; 95% C.I. 1.5-2; p<0.001), longer mean duration of previous bDMARDs (.5years: HR 4.1; 95% C.I. 3.5-4.7; p<0.001), and diagnosis (RA vs PSA: HR 1.22; 95% C.I. 1.02-1.47; p=0.030; RA vs axSpA: HR 0.89 95% C.I. 0.067-0.97; p=0.023; PSA vs axSpA: HR 0.66; 95% C.I. 0.57-0.77; p<0.001) (Fig 2).Figure 1.Kaplan-Meier curves for treatment survival, Log-rank test.Figure 2.Kaplan-Meier curves for treatment survival in all patients, Log-rank tesConclusion:BO-BS switch was undertaken in almost half of the patients. Patients with longer disease duration and longer bDMARD duration, were the most likely to be switched successfully to BS. BO-BS switching does not affect the survival of the treatment, indeed, it provides sustained effectiveness particularly if undertaken in patients with stable disease activity.Table 1.Factors associated with BO-BS switch, multivariate regression analysis.Disclosure of Interests:DAVIDE ASTORRI: None declared, Francesca Ometto: None declared, LARA FRISO: None declared, BERND RAFFEINER: None declared, Costantino Botsios: None declared, Andrea Doria Consultant of: GSK, Pfizer, Abbvie, Novartis, Ely Lilly, Speakers bureau: UCB pharma, GSK, Pfizer, Janssen, Abbvie, Novartis, Ely Lilly, BMS


2020 ◽  
Author(s):  
Viveka Björck ◽  
Lisa I Påhlman ◽  
Mikael Bodelsson ◽  
Ann_Cathrine Petersson ◽  
Thomas Kander

Abstract Background Group A streptococci (GAS) are known to cause serious invasive infections but little is known about outcomes when patients with these infections are admitted to intensive care. We wanted to describe critically ill patients with severe sepsis or septic shock due to invasive GAS (iGAS) and compare them with other patients with severe sepsis or septic shock. Methods Adult patients admitted to a general intensive care unit (ICU) in Sweden (2007-2019) were screened for severe sepsis or septic shock according to Sepsis 2 definition. Individuals with iGAS infection were identified. The outcome variables were mortality, days alive and free of vasopressors and invasive mechanical ventilation, maximum acute kidney injury score for creatinine, use of continuous renal replacement therapy and maximum sequential organ failure assessment score during the ICU stay. Age, simplified acute physiology score (SAPS 3) and iGAS were used as independent, explanatory variables in regression analysis. Cox regression was used for survival analyses. Results iGAS was identified in 53 of 1021 (5.2%) patients. Patients with iGAS presented lower median SAPS 3 score (62 [56–72]) vs 71 [61–81]), p < 0.001), had a higher frequency of cardiovascular cause of admission to the ICU (38 [72%] vs 145 [15%], p < 0.001) and had a higher median creatinine score (173 [100–311] vs 133 [86–208] µmol/L, p < 0.019). Of the GAS isolates, 50% were serotyped emm 1/T1 and this group showed signs of more pronounced circulatory and renal failure than patients with non- emm 1/T1, ( p = 0.036 and p = 0.007, respectively). After correction for severity of illness (SAPS 3) and age, iGAS infection was associated with lower mortality risk; 95% confidence interval (CI) of hazard ratio (HR) 0.204–0.746, p < 0.001. Morbidity analyses demonstrated that iGAS patients were more likely to develop renal failure. Conclusion Critically ill patients with iGAS infection had a lower mortality risk but a higher degree of renal failure compared to similarly ill sepsis patients. emm 1/T1 was found to be the most dominant serotype and patients with emm1 /T1 demonstrated more circulatory and renal failure than patients with other serotypes of iGAS.


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