Maya Hites - Academia.edu (original) (raw)

Papers by Maya Hites

Minerva anestesiologica

Although β--lactams are considered to have a safe therapeutic profile, neurotoxicity has been rep... more Although β--lactams are considered to have a safe therapeutic profile, neurotoxicity has been reported. The aim of this study was to assess the association between --lactam concentrations and neurological alterations in septic ICU patients.

Background: Altered pharmacokinetics (PK) of b-lactams in obese patients may result in inadequate... more Background: Altered pharmacokinetics (PK) of b-lactams in obese patients may result in inadequate serum concentrations when standard dosage regimens are administered. The aim of our study was to evaluate the effects of weight on cefuroxime (CEF) concentrations and PKs during surgical prophylaxis. Methods: Prospective observational study from 10/2012 to 4/2013 at Erasme hospital, including all consecutive adult patients undergoing gastric bypass or partial hepatectomy and receiving CEF for surgical prophylaxis. Patients were a priori stratified into 2 weight groups : < 100 (Group A), or ³ 100 kgs (Group B). Serum samples were obtained at baseline, 30 minutes, 1 hour(H), 2H, and 3H after a 30-minutes administration of 1.5 g of CEF, and at end of surgery. Drug levels were measured by HPLC-UV. Free CEF fraction (fCEF) was calculated assuming protein binding of 50%. Creatinine clearance was evaluated with 24H urine collects (CLcr(24H)). Adequacy of serum concentrations was defined as ...

Réanimation, 2015

ABSTRACT As the prevalence of obesity increases worldwide, clinicians will be more and more frequ... more ABSTRACT As the prevalence of obesity increases worldwide, clinicians will be more and more frequently confronted with obese, critically ill patients. Optimal administration of antibiotics is already a challenge in the critically ill patient because pharmacokinetics (PK) of antibiotics is often altered, and infections are more frequently caused by resistant pathogens than in the non-critically ill patient. Obesity per se may further alter the PK of antibiotics. This paper provides a narrative review of the potential PK changes of antibiotics in the obese, critically ill patient, and recommendations for optimal antibiotic therapy for the most frequently used antibiotics. However, these recommendations are essentially based on small sample-sized PK studies with no evaluation of outcome, and thus must be considered with caution. On one hand, critically ill patients may need higher than recommended regimens of β-lactams, linezolid, moxifloxacin, levofloxacin, tigecycline, and colistin; however, no further dose adjustment is necessary in obese, septic patients. Increased dosage regimens of β-lactams may be necessary only to treat obese, non-critically ill patients. On the opposite, dosage regimens should be based on total body weight for amikacin in patients with a body mass index (BMI) between 20 and 40 kg/m2, vancomycin, and daptomycin, and on adjusted body weight for ciprofloxacin, gentamycin, tobramycin, and amikacin in patients with a BMI greater than 40 kg/m2. Because of the lack of PK studies in this special patient population, and the large inter- and intraindividual PK drug variability in critically ill patients, we recommend therapeutic drug monitoring of all antibiotics administered, whenever possible, to optimize drug therapy. Résumé Comme la prévalence de l’obésité augmente dans le monde, le clinicien sera de plus en plus fréquemment confronté à des patients obèses en réanimation. Il est particulièrement difficile d’administrer des antibiotiques de façon optimale à ces patients, car la pharmacocinétique (PK) de ces médicaments est souvent altérée et les infections sont plus souvent dues à des bactéries multirésistantes que chez des patients en dehors des services de réanimation. L’obésité est un facteur supplémentaire, qui pourrait modifier la PK des antibiotiques. Cette mise au point discute des altérations PK des antibiotiques possibles chez l’individu obèse en réanimation et propose des recommandations susceptibles d’optimiser leur administration dans ce contexte. Néanmoins, ces recommandations sont fondées sur peu d’études, souvent de petite taille et qui n’évaluent pas l’impact clinique. Elles doivent être considérées avec prudence. S’il faut préconiser l’usage de doses plus importantes de β-lactames, linézolide, moxifloxacine, lévofloxacine, tigécycline et colistine chez le patient en état critique, l’obésité ne va pas modifier pour autant cette stratégie thérapeutique. Des doses plus élevées que chez le patient non obèse sont nécessaires pour les β-lactames en cas de traitement d’infections non compliquées. Les doses se fondent sur le poids total du patient pour la vancomycine, le daptomycine et l’amikacine quand l’indice de masse corporelle (IMC) est compris entre 20-40 kg/m2. Elles se fondent sur le poids ajusté pour la ciprofloxacine, la gentamicine, la tobramycine et l’amikacine si l’IMC est supérieur 40 kg/m2. Puisqu’il y a une paucité des études de PK des antibiotiques chez les patients obèses en état critique et que les patients en réanimation présentent une variabilité PK inter- et intra-individuelle importante, on recommande, si possible, de faire un monitorage thérapeutique de tout antibiotique administré pour optimiser l’antibiothérapie.

Journal de mycologie medicale, Jan 31, 2015

A patient with refractory diffuse lymphoma treated for pulmonary invasive aspergillosis developed... more A patient with refractory diffuse lymphoma treated for pulmonary invasive aspergillosis developed a concomitant primary cutaneous mucormycosis. The mucormycete was identified by sequencing as Mucor circinelloides. This case confirms the importance of a rapid pathogen diagnosis in immunocompromised patients and the usefulness of molecular methods for identification of rare fungal species.

Nutrition & diabetes, 2014

Obesity may alter the pharmacokinetics of β-lactams. The goal of this study was to evaluate if an... more Obesity may alter the pharmacokinetics of β-lactams. The goal of this study was to evaluate if and why serum concentrations are inadequate when standard β-lactam regimens are administered to obese, non-critically ill patients. During first year, we consecutively included infected, obese patients (body mass index (BMI) ⩾30 kg m(-2)) who received meropenem (MEM), piperacillin-tazobactam (TZP) or cefepime/ceftazidime (CEF). Patients with severe sepsis or septic shock, or those hospitalized in the intensive care unit were excluded. Serum drug concentrations were measured twice during the elimination phase by high-performance liquid chromatography. We evaluated whether free or total drug concentrations were >1 time (fT>minimal inhibition concentration (MIC)) or >4 times (T>4MIC) the clinical breakpoints for Pseudomonas aeruginosa during optimal periods of time: ⩾40% for MEM, ⩾50% for TZP and ⩾70% for CEF. We included 56 patients (median BMI: 36 kg m(-2)): 14 received MEM, 31 ...

Advanced Drug Delivery Reviews, 2014

The multiple organ dysfunction syndrome (MODS) is characterized by more than one organ system fai... more The multiple organ dysfunction syndrome (MODS) is characterized by more than one organ system failing, especially during critical illness. MODS is the leading cause of morbidity and mortality in current ICU practice; moreover, multiple organ dysfunction, especially liver and kidneys, may significantly affect the pharmacokinetics (PKs) of different drugs that are currently administered in critically ill patients. These PK alterations may either result in insufficient drug concentrations to achieve the desired effects or in blood and tissue accumulation, with the development of serious adverse events. The use of extra-corporeal circuits, such as extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT), may further contribute to PKs changes in this patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; population. In this review, we have described the main PK changes occurring in all these conditions and how drug concentrations may potentially be affected. The lack of prospective studies on large cohorts of patients makes impossible any specific recommendation on drug regimen adjustment in ICU patients. Nevertheless, the clinicians should be aware of these abnormalities in order to better understand some unexpected therapeutic issues occurring in such patients.

Current Infectious Disease Reports, 2011

Antibiotic treatment of critically ill patients remains a significant challenge. Optimal antibact... more Antibiotic treatment of critically ill patients remains a significant challenge. Optimal antibacterial strategy should achieve therapeutic drug concentration in the blood as well as the infected site. Achieving therapeutic drug concentrations is particularly difficult when infections are caused by some pathogens, such as Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative rods, because of their low susceptibility to antimicrobials. In sepsis, pharmacokinetics (PKs) of antibiotics are profoundly altered and may result in inadequate drug concentrations, even when recommended regimens are used, which potentially contribute to increased mortality and spread of resistance. The wide inter-individual PK variability observed in septic patients strongly limits the a priori prediction of the optimal dose that should be administered. Higher than standard dosages are necessary for the drugs, such as β-lactams, aminoglycosides, and glycopeptides, that are commonly used as first-line therapy in these patients to maximize their antibacterial activity. However, the benefit of reaching adequate drug concentrations on clinical outcome needs to be further determined.

Sexually Transmitted Diseases, 2014

We present the case of a man with a bicuspid aortic valve who presented with persistent fever. Bl... more We present the case of a man with a bicuspid aortic valve who presented with persistent fever. Blood cultures yielded Neisseria gonorrhoeae, and the diagnosis of infected mycotic aneurysm was confirmed by detection of the bacterial genome in the aortic wall. The patient was cured with surgery and intravenous ceftriaxone.

Talanta, 2013

A fast analytical procedure was developed for the simultaneous quantification of cefepime (CEF), ... more A fast analytical procedure was developed for the simultaneous quantification of cefepime (CEF), meropenem (MEM), ceftazidime (CZA), cefuroxime (CFX), aztreonam (AZT), and piperacillin (PIP) in serum of intensive care patients. The β-lactam pharmacokinetic parameters can be altered in severe sepsis due to changes in the distribution, the metabolism and the elimination process. Therapeutic drug monitoring (TDM) of β-lactams is therefore recommended in critically ill patients. The plasma samples were spiked with cefoperazone as internal standard and proteins were precipitated with methanol. The different β-lactams were separated with high performance liquid chromatography within 18 min, and quantified by UV spectrophotometry with a diode array detector. The method was validated by means of the accuracy profile approach based on β expectation tolerance intervals. The acceptance limits were settled at ± 30% according to the regulatory requirements. Assay validation demonstrated good performance for all β-lactams analyzed in terms of trueness, repeatability, linearity and intermediate precision over the range of 2-200 μg/mL. The simple extraction procedure provides respective absolute and relative recoveries ranging from 70% to 86% and from 66% to 89% for all the β-lactams analyzed. Few interferences were observed and the method was easily applicable to TDM in intensive care patients. The quantification of β-lactams should allow for antibiotic regimen adjustment in critically ill patients.

Journal of Antimicrobial Chemotherapy, 2013

Continuous infusion (CI) of high-dose vancomycin is often used to treat life-threatening infectio... more Continuous infusion (CI) of high-dose vancomycin is often used to treat life-threatening infections caused by less-susceptible Gram-positive bacteria. However, this approach has not been well studied in patients on continuous renal replacement therapy (CRRT). The aim of this study was to evaluate the adequacy of a new CI vancomycin regimen in septic patients undergoing CRRT. In this prospective study we measured vancomycin concentrations obtained with a new CI regimen for CRRT, which included a loading dose of 35 mg/kg given over a 4 h period followed by a daily dose of 14 mg/kg. Vancomycin concentrations were measured: at the end of the loading dose (T1); 12 h after the onset of therapy (T2); and 24 h after the onset of therapy (T3). Drug concentrations (at T2 and T3) were considered adequate if between 20 and 30 mg/L. CRRT intensity was calculated as: dialysate rate (mL/kg/h) + ultrafiltration rate (mL/kg/h). Vancomycin population pharmacokinetics were calculated using non-linear mixed-effects modelling. We studied 32 patients who received median (IQR) loading and daily vancomycin doses of 2750 mg (2250-3150) and 1100 mg (975-1270), respectively. Drug concentrations were: T1, 44 mg/L (38-58); T2, 27 mg/L (24-31); and T3, 23 mg/L (19-31). Vancomycin concentrations were adequate in 22/32 patients (69%) at T2 and in 20/32 (63%) at T3. The two relevant covariates that significantly affected drug concentrations were body weight and CRRT intensity. This new vancomycin regimen allowed the rapid achievement of target drug concentrations in the majority of patients. CRRT intensity had an influence on vancomycin clearance.

International Journal of Antimicrobial Agents, 2013

This study investigated whether variations in creatinine clearance (CLCr) are correlated with cha... more This study investigated whether variations in creatinine clearance (CLCr) are correlated with changes in β-lactam concentrations or pharmacokinetics in septic patients. Data for 56 adult patients admitted to the ICU in whom routine therapeutic drug monitoring (TDM) of broad-spectrum β-lactams (ceftazidime, cefepime, piperacillin or meropenem) was performed were reviewed. Patients were included if they had at least two TDM during their ICU stay for the same antibiotic and were not concomitantly treated with any extracorporeal replacement therapy. Serum drug concentrations were measured by HPLC-UV. Antibiotic pharmacokinetics were calculated using a one-compartment model and the percentage of time spent above four times the MIC (%T&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;4×MIC) for Pseudomonas aeruginosa and the antibiotic clearance (ATB-CL) were obtained. CLCr was measured on the same day as the TDM using 24-h urine collection. The %T&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;4×MIC and ATB-CL were significantly correlated with CLCr at the first (r=-0.41, P=0.002; r=0.56, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001, respectively) and second (r=-0.61, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001; r=0.63, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001, respectively) TDM. However, changes in ATB-CL were only weakly correlated with changes in CLCr (r=0.34, P=0.01). The proportion of patients with insufficient β-lactam concentrations at the first and second TDM were 39% and 30%, respectively, and increased proportionally to CLCr. Although CLCr was significantly correlated with concentrations and clearance of broad-spectrum β-lactams, changes in CLCr did not reliably predict variations in drug pharmacokinetics/pharmacodynamics. Routine TDM should be considered to adapt β-lactam doses in this setting.

Critical Care Medicine, 2013

Antimicrobial Agents and Chemotherapy, 2013

Antimicrobial Agents and Chemotherapy, 2010

Parallel administration of the proton pump inhibitor (PPI) esomeprazole has been shown to decreas... more Parallel administration of the proton pump inhibitor (PPI) esomeprazole has been shown to decrease oral bioavailability of posaconazole in healthy volunteers. We prospectively analyzed serum samples (n ‫؍‬ 59) obtained from hematology patients (n ‫؍‬ 27) under posaconazole prophylaxis. Patients treated concomitantly with pantoprazole had significantly lower posaconazole levels than patients without PPI treatment (median levels of 630 g/liter versus 1,125 g/liter, respectively). These results suggest that drug monitoring is relevant when posaconazole and pantoprazole are administered concomitantly.

Acta Clinica Belgica, 2007

We report an unusual association of T-cell lymphoma, autologous stem cell transplantation and Pro... more We report an unusual association of T-cell lymphoma, autologous stem cell transplantation and Progressive Multifocal Leukoencephalopathy.

Critical care (London, England), 2014

The use of standard doses of β-lactam antibiotics during continuous renal replacement therapy (CR... more The use of standard doses of β-lactam antibiotics during continuous renal replacement therapy (CRRT) may result in inadequate serum concentrations. The aim of this study was to evaluate the adequacy of unadjusted drug regimens (i.e., similar to those used in patients with normal renal function) in patients treated with CRRT and the influence of CRRT intensity on drug clearance. We reviewed data from 50 consecutive adult patients admitted to our Department of Intensive Care in whom routine therapeutic drug monitoring (TDM) of broad-spectrum β-lactam antibiotics (ceftazidime or cefepime, CEF; piperacillin/tazobactam; TZP; meropenem, MEM) was performed using unadjusted β-lactam antibiotics regimens (CEF = 2 g q8h; TZP = 4 g q6h; MEM = 1 g q8h). Serum drug concentrations were measured twice during the elimination phase by high-performance liquid chromatography (HPLC-UV). We considered therapy was adequate when serum drug concentrations were between 4 and 8 times the minimal inhibitory c...