-
1.
A pilot study of cystic fibrosis exacerbation response phenotypes reveals contrasting serum and sputum iron trends.
Gifford, AH, Polineni, D, He, J, D'Amico, JL, Dorman, DB, Williams, MA, Nymon, AB, Balwan, A, Budden, T, Zuckerman, JB
Scientific reports. 2021;(1):4897
Abstract
The cystic fibrosis (CF) community seeks to explain heterogeneous outcomes of pulmonary exacerbation (PEX) treatment. Serum and sputum inflammatory mediators may identify people with CF (PwCF) at risk for suboptimal responses. However, lack of an established association between response phenotypes and these mediators limits clinical application. In this pilot study, we prospectively characterized treatment response phenotypes by assessing health-related quality-of-life (HRQoL) during PEX. We also measured lung function and iron-related biochemical parameters in serum and sputum. We classified subjects as sustained symptom-responders (SRs) or non-sustained symptom-responders (NSRs) based on the absence or presence, respectively, of worsened symptom scores after initial improvement. We used linear mixed models (LMMs) to determine whether trends in lung function, hematologic, serum, and sputum indices of inflammation differed between response cohorts. In 20 PwCF, we identified 10 SRs and 10 NSRs with no significant differences in lung function at PEX onset and treatment durations. SRs had better model-predicted trends in lung function than NSRs during PEX. Non-linear trends in serum and sputum iron levels significantly differed between SRs and NSRs. In adults with cystic fibrosis, PEX treatment response phenotypes may be correlated with distinctive trends in serum and sputum iron concentrations.
-
2.
Optimizing Amoxicillin/Clavulanic Acid Dosing Regimens in Patients on Maintenance High-Flux Hemodialysis.
De Schuyter, K, Colin, PJ, Vanommeslaeghe, F, Delanghe, S, De Cock, P, Veys, N, De Paepe, P, Van Biesen, W, Eloot, S
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2021;(1):153-156
-
3.
Preconception exposure to over-the-counter medications and antibiotics and the risk of childhood asthma in Lebanon: A cross-sectional study.
Malaeb, D, Hallit, S, Sacre, H, Rahme, C, Malaeb, B, Hallit, R, Salameh, P
Allergologia et immunopathologia. 2021;(2):104-112
Abstract
OBJECTIVE The aim of this study was to elucidate the relationship between the mother's use of over-the-counter (OTC) medications during pregnancy and asthma in Lebanese children. METHODS A cross-sectional study was conducted on Lebanese students in both public and private schools, between January and September 2017, involving 1000 children aged between 4 and 17 years. RESULTS The intake of any medication as an independent variable throughout pregnancy reveals that being in a public school compared to a private one (Beta = 0.344) and breastfeeding (Beta = 0.51) were highly associated with lower odds of asthma, while having a positive family of allergic rhinitis (Beta = 2.129) and the intake of any medication during pregnancy (Beta = 7.052) were highly associated with higher odds of asthma.A second logistic regression, taking as the dependent variable asthmatic versus healthy children and taking each OTC drug as an independent variable, showed that taking paracetamol once per week during pregnancy (Beta = 4.66) and proton pump inhibitors (PPIs) once per month (Beta = 3.498) compared to no intake were significantly correlated with higher probability of asthma. CONCLUSION Our findings showed that the intake of paracetamol, vitamin C, and PPIs during pregnancy is strongly correlated with asthma in the offspring. Since these factors are avoidable, it is necessary to raise awareness among healthcare professionals to reduce the prevalence of asthma in children.
-
4.
Real-Life Safety and Effectiveness of Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis.
Burgel, PR, Munck, A, Durieu, I, Chiron, R, Mely, L, Prevotat, A, Murris-Espin, M, Porzio, M, Abely, M, Reix, P, et al
American journal of respiratory and critical care medicine. 2020;(2):188-197
Abstract
Rationale: Lumacaftor-ivacaftor is a CFTR (cystic fibrosis transmembrane conductance regulator) modulator combination recently approved for patients with cystic fibrosis (CF) homozygous for the Phe508del mutation.Objectives: To evaluate the safety and effectiveness of lumacaftor-ivacaftor in adolescents (≥12 yr) and adults (≥18 yr) in a real-life postapproval setting.Methods: The study was conducted in the 47 CF reference centers in France. All patients who initiated lumacaftor-ivacaftor from January 1 to December 31, 2016, were eligible. Patients were evaluated for lumacaftor-ivacaftor safety and effectiveness over the first year of treatment following the French CF Learning Society's recommendations.Measurements and Main Results: Among the 845 patients (292 adolescents and 553 adults) who initiated lumacaftor-ivacaftor, 18.2% (154 patients) discontinued treatment, often owing to respiratory (48.1%, 74 patients) or nonrespiratory (27.9%, 43 patients) adverse events. In multivariable logistic regression, factors associated with increased rates of discontinuation included adult age group, percent predicted FEV1 (ppFEV1) less than 40%, and numbers of intravenous antibiotic courses during the year before lumacaftor-ivacaftor initiation. Patients with continuous exposure to lumacaftor-ivacaftor showed an absolute increase in ppFEV1 (+3.67%), an increase in body mass index (+0.73 kg/m2), and a decrease in intravenous antibiotic courses by 35%. Patients who discontinued treatment had significant decrease in ppFEV1, without improvement in body mass index or decrease in intravenous antibiotic courses.Conclusions: Lumacaftor-ivacaftor was associated with improvement in lung disease and nutritional status in patients who tolerated treatment. Adults who discontinued lumacaftor-ivacaftor, often owing to adverse events, were found at high risk of clinical deterioration.
-
5.
Evaluating the risk of hyperkalaemia and acute kidney injury with cotrimoxazole: a retrospective observational study.
Rajput, J, Moore, LSP, Mughal, N, Hughes, S
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. 2020;(12):1651-1657
Abstract
OBJECTIVES Increasing antimicrobial resistance has renewed interest in older, less used antimicrobials. Cotrimoxazole shows promise; however, hyperkalaemia and acute kidney injury (AKI) are potential complications. Identifying risk factors for and quantification of these events is required for safe use. This study aimed to evaluate predictors of cotrimoxazole-associated AKI and hyperkalaemia in a clinical setting. METHODS Patients prescribed cotrimoxazole were identified using electronic healthcare records over 3 years (1 April 2016 to 31 March 2019). Individual risk factors were recognized. Serum creatinine and potassium trends were analysed over the subsequent 21 days. AKI and patients with hyperkalaemia were classified using Kidney Disease Improving Global Outcomes (KDIGO) and laboratory criteria. Univariate and multiple logistic regression analyses were performed. RESULTS Among 214 patients prescribed cotrimoxazole, 42 (19.6%, 95% confidence interval (CI) 14.6-25.7) met AKI criteria and 33 (15.4%, 95% CI 11.0-21.1) developed hyperkalaemia. Low baseline estimated glomerular filtration rate (<60 mL/min/1.73 m2, odds ratio (OR) 7.78, 95% CI 3.57-16.13, p < 0.0001) and cardiac disorders (OR 2.40, 95% CI 1.17-4.82, p 0.011) predicted AKI, while low baseline estimated glomerular filtration rate (<60 mL/min/1.73 m2, OR 6.80, 95% CI 3.09-15.06, p < 0.0001) and higher baseline serum potassium (p 0.001) predicted hyperkalaemia. Low-dose cotrimoxazole (<1920 mg/d) was associated with lower AKI and hyperkalaemia risk (p 0.007 and 0.019 respectively). Early (within the first 2-4 days of therapy) serum creatinine changes predicted AKI (OR 3.65, 95% CI 1.73-7.41, p 0.001), and early serum potassium changes predicted hyperkalaemia (>0.6 mmol/L, OR 2.47, 95% CI 1.14-5.27, p 0.0236). CONCLUSIONS Cotrimoxazole-associated AKI and hyperkalaemia is frequent and dose dependent. Renal function, serum potassium and preexisting cardiac disorders should be evaluated before prescribing cotrimoxazole. Serum creatinine and potassium monitoring within first 2 to 4 days of treatment to identify susceptible patients is recommended, and the lowest effective dose ought to be prescribed.
-
6.
Clinical and subclinical acute kidney injury in multidrug-resistant septic patients treated with colistimethate sodium: Incidence and clinical outcomes.
Thammathiwat, T, Tiranathanagul, K, Srisawat, N, Susantitaphong, P, Praditpornsilpa, K, Eiam-Ong, S
Nephrology (Carlton, Vic.). 2020;(1):32-39
Abstract
AIM: Colistimethate sodium (CMS) has been postulated as the principal cause of high incidence of clinical acute kidney injury (AKI) in multidrug-resistance (MDR) septic patients with normal baseline serum creatinine (sCr) who were treated with CMS. This prospective observational study was conducted to examine the incidence and clinical outcomes of clinical and subclinical AKI in MDR septic patients receiving CMS. METHODS Forty-two MDR septic patients with normal sCr who required CMS were included. Clinical AKI was diagnosed by increased sCr levels according to the KDIGO2012 criteria while subclinical AKI was identified by elevated levels of urinary neutrophil gelatinase-associated lipocalin (uNGAL > 150 ng/mL) or urinary liver-type fatty-acid-binding protein (uL-FABP > 10.5 ng/mL). RESULTS Clinical AKI was noted in 47.6% of patients on day 5 and 38.1% on day 7 after initiating CMS. By using uL-FABP, subclinical AKI was observed in 45.2% and 54.8% on day 5 and 7, respectively. At baseline prior to CMS treatment, subclinical AKI was already present in 90%. The baseline uL-FABP was superior to the baseline uNGAL in early prediction of clinical AKI on day 5. The subclinical AKI patients had comparable worse outcomes as clinical AKI patients. CONCLUSION The incidence of subclinical AKI in MDR septic patients before CMS treatment was extremely high. The baseline uL-FABP provided the best predictive capacity of clinical AKI. The causes of clinical AKI might include the persistence of sepsis process, subclinical AKI and CMS nephrotoxicity. Proper management of subclinical AKI patients before CMS initiation should be concerned to prevent further renal damage and improve patient and renal outcomes.
-
7.
High prevalence of MDR gram-negative bacteria in feces of healthy blood donors in Mexico.
Tamez-Torres, KM, Ponce-de-Leon, A, Torres-Gonzalez, P, Perez-Garcia, E, Torres-Veintimilla, E, Valle, MB, Sifuentes-Osornio, J
European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. 2020;(8):1439-1444
Abstract
During the initial stage of a study to recruit universal intestinal microbiota donors in Mexico City, we found multiple "healthy" subjects that colonized with MDRO (Multidrug-resistant organisms). We aimed to describe clinical and demographic characteristics of these individuals. This was a prospective observational study. Participants were consecutively recruited among blood donors. A fecal sample was collected from each subject and analyzed at the same day in search of MDRO through chromographic culture media and, if growth observed, later confirmed by MALDI-TOF and susceptibility testing in Vitek 2 system. From July 2018 to March 2019, 85 individuals were screened for fecal colonization. Median age was 35 years (IQR 27-46 years), and 48/85 (56.4%) were males. Seventy-two (84.7%) subjects harbored at least one MDRO. ESBL-producing microorganisms were found in 72/85 (84.3%) subjects, and E. coli was the most frequent (63/85, 74.1%). Four samples (2 E. coli, 2 P. aeruginosa, 2.4% each) harbored carbapenem-resistant Enterobacteriaceae (CRE), together with an ESBL-producing microorganism. Antibiotic use (p = 0.06) and PPIs or H2-blockers intake (p = 0.03) were more common in the colonized subjects during the previous 6-month period. We report a high incidence of enteric colonization of healthy subjects with MDRO, a condition that may be related to antibiotics or PPIs/H2-blockers consumption. This surprisingly high MDRO colonization rate in potential FMT donors emphasizes the need for careful screening of donors to avoid possible transmission to FMT recipients.
-
8.
Helicobacter pylori eradication increases the serum high density lipoprotein cholesterol level in the infected patients with chronic gastritis: A single-center observational study.
Iwai, N, Okuda, T, Oka, K, Hara, T, Inada, Y, Tsuji, T, Komaki, T, Inoue, K, Dohi, O, Konishi, H, et al
PloS one. 2019;(8):e0221349
Abstract
BACKGROUND Extra-gastric manifestation of Helicobacter pylori infection involves systemic inflammation, which results in the production of several cytokines. Only a few clinical trials have investigated the effect of H. pylori eradication therapy on lipid metabolism in the infected patients with chronic gastritis. We aimed to evaluate the effect of H. pylori eradication therapy on lipid metabolism in a Japanese population with chronic gastritis. METHODS One hundred and sixty-three patients with H. pylori-associated chronic gastritis were enrolled in this study between June 2015 and March 2017. They underwent H. pylori eradication therapy; the effects of the therapy were assessed by the urea breath test performed at least 4 weeks after the therapy. After confirming H. pylori eradication, the health screening examination was repeated between May 2016 and August 2018. The clinical parameters were compared before and after the administration of the eradication therapy. RESULTS The mean age of the enrolled patients was 56.7 years, and the mean follow-up duration was 514.7 days. Weight, body mass index, and obesity index were significantly increased post-eradication therapy compared to those pre-eradication therapy. White blood cell and platelet counts were significantly decreased, and high density lipoprotein cholesterol (HDL) level was significantly increased (P = 0.001), while low density lipoprotein cholesterol (LDL), total cholesterol, and triglycerides levels were not altered significantly. Hence, the LDL/HDL ratio was significantly decreased. CONCLUSIONS This study reported that H. pylori eradication therapy increase the HDL levels in the infected patients with chronic gastritis. Hence, the LDL/HDL ratio, which is used to evaluate the risk of atherosclerosis, was significantly decreased post-eradication therapy compared to that pre-eradication therapy.
-
9.
Amoxicillin/clavulanic acid+aminoglycoside as empirical antibiotic treatment in severe community-acquired infections with diagnostic uncertainty.
Courjon, J, Chirio, D, Demonchy, E, Michelangeli, C, Degand, N, Roger, PM
European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. 2019;(5):895-901
Abstract
Diagnostic uncertainty is common in the emergency room and multidrug-resistant bacteria emerge in the community setting, implying to establish the most efficient empirical antibiotic therapy (eEAT). Our aim was to identify such eEAT, considering that in case of DU with severe clinical presentation, most prescribers would propose an empiric combination (EC). The medical dashboard of our ward records prospectively 28 characteristics of each hospitalization including hospitalization motive, final diagnosis, and all antibiotics prescribed. All patients with community-acquired bacteremia (CAB) were included. DU was defined by a discrepancy between suspected diagnosis in the emergency room and final diagnosis. eEAT was defined by in vitro activity of at least one prescribed compound. Finally, independently from the dashboard, we retrospectively compared 2 CTs: amoxicillin/clavulanic acid (AMC)+gentamicin (G) and cefotaxime (3GC)+G. One thousand thirty-four patients with a final diagnosis of CAB were identified from July 2005 to June 2018, including 357 DU (35%) at baseline. eEAT (n = 553) was associated with a trend towards a lower death rate compared to inefficient therapies: 5.4 vs 10.0% (p = 0.053), and effective antibiotic reassessment was the most protective factor against an unfavorable outcome: 0.34 (0.16-0.71). Bacteria involved in case of UD were resistant to AMC+G and to 3GC+G in 8.1% and 12.8% of patients, respectively. Diagnostic uncertainty was a frequent event requiring antibiotic reassessment. As the latter was not systematically realized, the best eEAT is required and AMC+aminoglycoside should be considered.
-
10.
[Infections in diabetic foot. Choice of empirical antibiotic regimen].
Carro, GV, Carlucci, E, Priore, G, Gette, F, Llanos, MLA, Dicatarina Losada, MV, Noli, ML, Amato, PS
Medicina. 2019;(3):167-173
Abstract
Diabetic foot infections are related to severe complications and constitute the main reason for diabetes-related hospitalization and lower limb amputations. A diabetic foot infection requires prompt actions to avoid progression of the infected wound; a soft tissue sample has to be taken for microbiological culture and empiric antibiotic therapy must be started immediately. Empiric antibiotic schemes should be chosen based on the severity of the infection and the local prevalence of microbial causal agents. Therefore, it is important to monitor these indicators. The aim of this study was to determine which microorganisms were more prevalent in cultures of diabetic foot infections during 2018 and what antibiotic combination was better to cover local microbiology, compared with data available from 2015 for a similar cohort. A total of 68 positive cultures were obtained of 72 soft tissue specimens analyzed. The most frequent microorganisms were Gram negative (47.1%), and resulted significantly more frequent than in 2015 (24.6%) p = 0.01. These Gram negative germs also resulted more sensitive to ciprofloxacin than in 2015 (62.5% vs. 25.0%) p = 0.03. Amoxicillin-clavulanate plus ciprofloxacin was the optimal combination therapy in 2018, while in 2015 it was amoxicillin-clavulanate plus trimethoprim sulfamethoxazole. In agreement with these results, we recommend amoxicillin-clavulanate plus ciprofloxacin as the empiric antibiotic regimen of choice for soft tissue infections in diabetic foot. We consider surveillance of local microbiology to be an important tool in the management of diabetic foot infections.