The global burden associated with antimicrobial resistance is of increasing concern. The aim of this study was to evaluate risk factors associated with multidrug-resistant (MDR) infection and its ...clinical impact in a cohort of patients with healthcare-associated (HCA) bacteremic urinary tract infections (BUTI).INTRODUCTIONThe global burden associated with antimicrobial resistance is of increasing concern. The aim of this study was to evaluate risk factors associated with multidrug-resistant (MDR) infection and its clinical impact in a cohort of patients with healthcare-associated (HCA) bacteremic urinary tract infections (BUTI).This is a post-hoc analysis a prospective multicenter study of patients with HCA-BUTI (ITUBRAS-2). The primary outcome was MDR profile. Secondary outcomes were clinical response (at 48-72h and at hospital discharge) and length of hospital stay from onset of BUTI. Logistic regression was used to evaluate variables associated with MDR profile and clinical response. Length of hospital stay was evaluated using multivariate median regression.METHODSThis is a post-hoc analysis a prospective multicenter study of patients with HCA-BUTI (ITUBRAS-2). The primary outcome was MDR profile. Secondary outcomes were clinical response (at 48-72h and at hospital discharge) and length of hospital stay from onset of BUTI. Logistic regression was used to evaluate variables associated with MDR profile and clinical response. Length of hospital stay was evaluated using multivariate median regression.443 episodes were included, of which 271 (61.17%) were classified as expressing an MDR profile. In univariate analysis, MDR profile was associated with E. coli episodes (OR 3.13, 95% CI 2.11-4.69, p<0.001) and the extensively drug-resistant (XDR) pattern with P. aeruginosa etiology (OR 7.84, 95% CI 2.37-25.95; p=0.001). MDR was independently associated with prior use of fluoroquinolones (aOR 2.43; 95% CI 1.25-4.69), cephalosporins (aOR 2.14; 95% CI 1.35-3.41) and imipenem or meropenem (aOR 2.08; 95% CI 1.03-4.20) but not with prior ertapenem. In terms of outcomes, MDR profile was not associated with lower frequency of clinical cure, but with longer hospital stay.RESULTS443 episodes were included, of which 271 (61.17%) were classified as expressing an MDR profile. In univariate analysis, MDR profile was associated with E. coli episodes (OR 3.13, 95% CI 2.11-4.69, p<0.001) and the extensively drug-resistant (XDR) pattern with P. aeruginosa etiology (OR 7.84, 95% CI 2.37-25.95; p=0.001). MDR was independently associated with prior use of fluoroquinolones (aOR 2.43; 95% CI 1.25-4.69), cephalosporins (aOR 2.14; 95% CI 1.35-3.41) and imipenem or meropenem (aOR 2.08; 95% CI 1.03-4.20) but not with prior ertapenem. In terms of outcomes, MDR profile was not associated with lower frequency of clinical cure, but with longer hospital stay.MDR profile was independently associated with prior use of fluoroquinolones, cephalosporins, imipenem and meropenem, but not with prior ertapenem. MDR-BUTI episodes were not associated with worse clinical cure, although was independently associated with longer duration of hospital stay.CONCLUSIONSMDR profile was independently associated with prior use of fluoroquinolones, cephalosporins, imipenem and meropenem, but not with prior ertapenem. MDR-BUTI episodes were not associated with worse clinical cure, although was independently associated with longer duration of hospital stay.
This study correlates in vivo findings in a patient with an extensively drug-resistant (XDR) P. aeruginosa infection who developed resistance to ceftazidime-avibactam (CAZ-AVI) with in vitro results ...of a 7-day hollow-fiber infection model (HFIM) testing the same bacterial strain. The patient was critically ill with ventilator-associated pneumonia caused by XDR P. aeruginosa ST175 with CAZ-AVI MIC of 6 mg/L and was treated with CAZ-AVI in continuous infusion at doses adjusted for renal function. Plasma concentrations of CAZ-AVI were analyzed on days 3, 7, and 10. In the HIFM, the efficacy of different steady-state concentrations (Css) of CAZ-AVI (12, 18, 30 and 48 mg/L) was evaluated. In both models, a correlation was observed between the decreasing plasma levels of CAZ-AVI and the emergence of resistance. In the HIFM, a Css of 30 and 48 mg/L (corresponding to 5× and 8× MIC) had a bactericidal effect without selecting resistant mutants, whereas a Css of 12 and 18 mg/L (corresponding to 2× and 3× MIC) failed to prevent the emergence of resistance. CAZ/AVI resistance development was caused by the selection of a single ampC mutation in both patient and HFIM. Until further data are available, strategies to achieve plasma CAZ-AVI levels at least 4× MIC could be of interest, particularly in severe and high-inoculum infections caused by XDR P. aeruginosa with high CAZ-AVI MICs.
Antibiotic allergy labels (AAL) are related to worse therapeutic results. Strategies to improve the management of these patients, such as the implementation of antibiotic desensitization, are ...essential for Antimicrobial Stewardship Programs (ASP). The aim of our study is to evaluate the efficacy and safety of antibiotic desensitization procedures for the management of patients with AAL.
A retrospective study from 2015 to 2022 was performed to describe all antibiotic desensitization conducted in our institution, within the framework of ASP. A systematic literature review using electronic databases, such as PubMed, was also done to identify studies describing antibiotic desensitization between 2000 and 2022.
Sixteen antibiotic desensitization protocols were carried out in our institution. In fourteen cases, the desensitization was successfully completed, and the antibiotic could be used to treat the infection. In the systematic review, twenty-two studies were included, with a total of 202 desensitization episodes . In 97% of them, the desensitization was completed successfully. No desensitization-related mortality was observed neither in our cohort nor in literature review.
Antibiotic desensitization strategies should be considered a safe and effective tool that can be included in ASP for patients with a high risk of or confirmed allergy to penicillin.
A liver stiffness below 21 kPa has a high negative predictive value to exclude the presence of esophageal varices at risk of bleeding in HIV/hepatitis C virus (HCV)-coinfected patients. Consequently, ...upper gastrointestinal endoscopy (UGE) for the screening of esophageal varices could be avoided in these patients. However, this strategy has not been widely accepted due to concerns about its safety.
To assess the ability of liver stiffness to predict the risk of portal hypertensive gastrointestinal bleeding (PHGB) in HIV/HCV-coinfected patients with compensated cirrhosis.
Prospective study of 446 HIV/HCV-coinfected patients with a new diagnosis of cirrhosis and no previous decompensation. All patients underwent a UGE for the screening of esophageal varices at entry in the cohort before November 2009. From this date, UGE was not recommended in patients with liver stiffness below 21 kPa. The time from diagnosis of cirrhosis to the emergence of PHGB was evaluated.
After a median (quartile1-quartile3) follow-up of 49 (25-68) months, 15 (3.4%, 95% confidence interval 1.7-5%) patients developed a first PHGB episode. In all cases, baseline liver stiffness was at least 21 kPa. Thus, the negative predictive value of a liver stiffness below 21 kPa to predict PHGB during follow-up was 100%. At the time of the bleeding episode, liver stiffness was above this threshold in all patients.
Liver stiffness identifies HIV/HCV-coinfected patients with compensated cirrhosis with a very low risk of PHGB. In fact, no individual with liver stiffness below 21 kPa developed this outcome. Our results confirm that UGE can be safely spared in patients with liver stiffness below 21 kPa.
Background
CD4/CD8 ratio has been used as a quantitative prognostic risk factor in patients with viral infections. This study aims to assess the association between in-hospital mortality and at ...admission CD4/CD8 ratio among individuals with acute SARS-CoV-2 infection.
Methods
This is a longitudinal cohort study with data of all consecutive patients admitted to the COVID-19 unit at Hospital del Mar, Barcelona, Spain for ≥48 h between March to May 2020. The CD4+ CD8+ T-cell subset differentiation was assessed by flow cytometry at admission as well as a complete blood test. Patients were classified according to CD4/CD8 ratio tertiles. The primary outcome was in-hospital mortality and the secondary outcome was acute respiratory distress (ARDS).
Results
A total of 338 patients were included in the cohort. A high CD4/CD8 ratio (third tertile) was associated with a higher in-hospital mortality adjusted Cox model hazard ratio (HR) 4.68 (95%CI 1.56–14.04,
p
= 0.006), reference: second tertile HR 1. Similarly, a high CD4/CD8 ratio (third tertile) was associated with a higher incidence of ARDS adjusted logistic regression model OR 1.97 (95%CI 1.11–3.55,
p
= 0.022) reference: second tertile HR 1. There was a trend of higher in-hospital mortality and incidence of ARDS in patients within the first tertile of CD4/CD8 ratio compared with the second one, but the difference was not significant. No associations were found with total lymphocyte count or inflammatory parameters, including D-dimer.
Conclusion
CD4/CD8 ratio is a prognostic factor for the severity of COVID-19, reflecting the negative impact on prognosis of those individuals whose immune response has abnormal CD8+ T-cell expansion during the early response to the infection.
To design a randomized clinical trial to assess the efficacy and safety of favipiravir in patients with COVID-19 disease with pneumonia.
A randomized, double blind, placebo-controlled clinical trial ...of favipiravir in patients with COVID-19 pneumonia was conducted in three Spanish sites. Randomization 1:1 to favipiravir or placebo (in both groups added to the Standard of Care) was performed to treat the patients with COVID-19 pneumonia. The primary endpoint was "time to clinical improvement," measured as an improvement for ≥ two categories on a 7-point WHO ordinal scale in an up to 28 days' time frame.
Forty-four patients were randomized (23 in the favipiravir group and 21 in the placebo group). The median time to clinical improvement was not different between the favipiravir and the placebo arms (10 days for both groups) and none of the secondary endpoints showed significant differences between arms. The proportion of adverse events (both serious and non-serious) was statistically different between the favipiravir group (68.29%) and the placebo group (31.7%) (p = 0.019), but there was insufficient statistical evidence to correlate the degree of severity of the events with the treatment group.
Favipiravir administered for ten days to patients with COVID-19 and pneumonia did not improve outcomes compared with placebo. Although this is an underpowered negative study, efficacy results align with other randomized trials. However, in the present study, the non-serious adverse events were more frequent in the favipiravir group.
Introduction
Extensively drug-resistant (XDR)
Pseudomonas aeruginosa
(PA) infections are difficult to treat. We aimed to compare aminoglycosides or polymyxin monotherapy versus other antibiotic ...regimens (carbapenems, aztreonam, ceftazidime, cefepime, ceftolozane-tazobactam, or ceftazidime-avibactam) in complicated urinary tract infections (cUTI) caused by XDR-PA.
Methods
Study performed at a tertiary-care hospital from 2010 to 2019. All consecutive adult patients with XDR-PA urine cultures and diagnosed with cUTI were retrospectively reviewed. XDR phenotype was defined according to Magiorakos et al. A propensity score was used as a covariate in multivariate analyses and for matching. Primary outcome was early clinical failure and at end of treatment (EOT). Main secondary outcomes were 30- and 90-day mortality, microbiological clearance, and antibiotic-related side effects.
Results
Of the 465 episodes screened, 101 were included, 48% were treated with aminoglycoside or colistin monotherapy. Most XDR-PA were susceptible to colistin (100%) and amikacin (43%). Patients treated with antibiotic regimens other than aminoglycosides or polymyxin monotherapy were more likely to have hematologic malignancy (
p
< 0.001), higher SOFA score (
p
= 0.048), and bacteremia (
p
= 0.003). In multivariate models adjusted by propensity score, aminoglycoside or colistin monotherapy was not associated with worse outcomes. After propensity score matching, 28 episodes in each treatment group were matched. Adjusted ORs (95% CI) for early clinical failure and at EOT with aminoglycosides or polymyxin monotherapy were 0.53 (0.18–1.58) and 1.29 (0.34–4.83), respectively. Aminoglycoside or colistin monotherapy was not associated with higher 30-day (HR 0.93, 95% CI 0.17–5.08) or 90-day mortality (HR 0.68, 95% CI 0.20–2.31), nor with absence of microbiological clearance (OR 0.72, 95% CI 0.33–1.58). No statistically significant differences were found in terms of nephrotoxicity.
Clostridioides difficile
infection was observed only in the “other antibiotic regimens” group (
n
= 6, 11.3%).
Conclusions
Aminoglycosides or polymyxin monotherapy showed good efficacy and safety profile in treating cUTI caused by XDR-PA. These results may be useful for antibiotic stewardship activities.
Introduction
Healthcare-associated (HCA) infections represent a growing public health problem. The aim of this study was to compare community-onset healthcare associated (CO-HCA) bacteremic urinary ...tract infections (BUTI) and hospital-acquired (HA)-BUTI with special focus on multidrug resistances (MDR) and outcomes.
Methods
ITUBRAS-project is a prospective multicenter cohort study of patients with HCA-BUTI. All consecutive hospitalized adult patients with CO-HCA-BUTI or HA-BUTI episode were included in the study. Exclusion criteria were: patients < 18 years old, non-hospitalized patients, bacteremia from another source or primary bacteremia, non-healthcare-related infections and infections caused by unusual pathogens of the urinary tract. The main outcome variable was 30-day all-cause mortality with day 1 as the first day of positive blood culture. Logistic regression was used to analyze factors associated with clinical cure at hospital discharge and with receiving inappropriate initial antibiotic treatment. Cox regression was used to evaluate 30-day all-cause mortality.
Results
Four hundred forty-three episodes were included, 223 CO-HCA-BUTI. Patients with CO-HCA-BUTI were older (
p
< 0.001) and had more underlying diseases (
p
= 0.029) than those with HA-BUTI. The severity of the acute illness (Pitt score) was also higher in CO-HCA-BUTI (
p
= 0.026). Overall, a very high rate of MDR profiles (271/443, 61.2%) was observed, with no statistical differences between groups. In multivariable analysis, inadequate empirical treatment was associated with MDR profile (aOR 3.35; 95% CI 1.77–6.35),
Pseudomonas aeruginosa
(aOR 2.86; 95% CI 1.27–6.44) and Charlson index (aOR 1.11; 95% CI 1.01–1.23). Mortality was not associated with the site of acquisition of the infection or the presence of MDR profile. However, in the logistic regression analyses patients with CO-HCA-BUTI (aOR 0.61; 95% CI 0.40–0.93) were less likely to present clinical cure.
Conclusion
The rate of MDR infections was worryingly high in our study. No differences in MDR rates were found between CO-HCA-BUTI and HA-BUTI, in the probability of receiving inappropriate empirical treatment or in 30-day mortality. However, CO-HCA-BUTIs were associated with worse clinical cure.
Objective: The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most frequent cause of euvolemic hyponatremia. We present a case of an extremely rare tumor in adults along with ...SIADH, as well a review of the literature.Methods: A 67-year-old woman was hospitalized following detection of a serum sodium (SNa) level of 112 mmol/L. SIADH of unknown etiology was diagnosed and fluid restriction was initiated, with a partial response. A computed tomography (CT) scan revealed small thoracic nodes as the only finding. The patient was discharged and referred for outpatient follow-up (SNa, 126 mmol/L). After 6 months, chest CT scan and laboratory testing were repeated, with similar results. After a 2-year follow-up, the patient presented with marked weakness again. SNa was 132 mmol/L. Tolvaptan was initiated, with a final dose of 60 mg, with a subsequent 4 mmol/L rise in SNa and excellent tolerance. One year after tolvaptan was started, the patient was hospitalized with severe hyponatremia (115 mmol/L).Results: A chest CT scan showed a mediastinal mass located in the thymus. Vasopressin (AVP) concentration was extremely elevated. The patient underwent tumor resection and was diagnosed with adult neuroblastoma. SNa levels, blood osmolality, and plasma AVP concentration completely normalized 2 weeks after tumor removal.Conclusion: Follow-up and periodic screening for cancer should be considered in long-standing SIADH of unknown etiology. Some patients with extremely high AVP levels may not respond/maintain response to tolvaptan therapy. Determination of AVP levels may be helpful for the management of SIADH in these patients.Abbreviations: AVP = vasopressin CT = computed tomography POSM = plasma osmolality SIADH = syndrome of inappropriate antidiuretic hormone secretion SNa = serum sodium UOSM = urine osmolality
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