scholarly journals Population pharmacokinetics and outcomes of critically ill pediatric patients treated with intravenous colistin at higher than recommended doses

2021 ◽  
Author(s):  
Charalampos Antachopoulos ◽  
Anastasia Geladari ◽  
Cornelia B Landersdorfer ◽  
Eleni Volakli ◽  
Stavroula Ilia ◽  
...  
Keyword(s):  
Creatinine Clearance ◽  
Critically Ill ◽  
Ultra Performance Liquid Chromatography ◽  
European Medicines Agency ◽  
Carbapenem Resistant ◽  
Apparent Clearance ◽  
Colistimethate Sodium ◽  
Disposition Model ◽  
The Relationship ◽  
State Concentration

Limited pharmacokinetic (PK) data suggest that currently recommended pediatric dosages of colistimethate sodium (CMS) by the Food and Drug Administration and European Medicines Agency may lead to suboptimal exposure, resulting in plasma colistin concentrations frequently <2 mg/L. We conducted a population PK study in 17 critically ill patients 3 months-13.75 years (median 3.3 years) old, who received CMS for infections caused by carbapenem-resistant Gram-negative bacteria. CMS was dosed at 200,000 IU/kg/d [6.6 mg colistin base activity (CBA)/kg/d, 6 patients], 300,000 IU/kg/d (9.9 mg CBA/kg/d, 10 patients) and 350,000 IU/kg/d (11.6 mg CBA/kg/d, 1 patient). Plasma colistin concentrations were determined using ultra-performance liquid chromatography combined with electrospray ionization tandem mass spectrometry. Colistin PK was described by a one-compartment disposition model including creatinine clearance, body weight and the presence or absence of systemic inflammatory response syndrome (SIRS) as covariates (p<0.05 for each). The average colistin plasma steady-state concentration (Css,avg) ranged from 1.11-8.47 mg/L (median 2.92 mg/L). Ten patients had Css,avg ≥2 mg/L. The presence of SIRS was associated with decreased apparent clearance of colistin (47.8% of that without SIRS). The relationship between the mg/day of CBA to achieve each 1 mg/L of plasma colistin Css,avg and creatinine clearance (mL/min) was described by linear regression with different slopes for patients with and without SIRS. Nephrotoxicity, probably colistin-unrelated, was observed in one patient. In conclusion, administration of CMS at the above doses improved exposure and was well tolerated. Apparent clearance of colistin was influenced by creatinine clearance and the presence or absence of SIRS.

scholarly journals Etiology, incidence, and outcomes of patient–ventilator asynchrony in critically-ill patients undergoing invasive mechanical ventilation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yongfang Zhou ◽  
Steven R. Holets ◽  
Man Li ◽  
Gustavo A. Cortes-Puentes ◽  
Todd J. Meyer ◽  
...  
Keyword(s):  
Risk Factors ◽  
Mechanical Ventilation ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Invasive Mechanical Ventilation ◽  
Surgical Intensive Care ◽  
Mechanically Ventilated ◽  
History Of ◽  
Training Background ◽  
The Relationship

AbstractPatient–ventilator asynchrony (PVA) is commonly encountered during mechanical ventilation of critically ill patients. Estimates of PVA incidence vary widely. Type, risk factors, and consequences of PVA remain unclear. We aimed to measure the incidence and identify types of PVA, characterize risk factors for development, and explore the relationship between PVA and outcome among critically ill, mechanically ventilated adult patients admitted to medical, surgical, and medical-surgical intensive care units in a large academic institution staffed with varying provider training background. A single center, retrospective cohort study of all adult critically ill patients undergoing invasive mechanical ventilation for ≥ 12 h. A total of 676 patients who underwent 696 episodes of mechanical ventilation were included. Overall PVA occurred in 170 (24%) episodes. Double triggering 92(13%) was most common, followed by flow starvation 73(10%). A history of smoking, and pneumonia, sepsis, or ARDS were risk factors for overall PVA and double triggering (all P < 0.05). Compared with volume targeted ventilation, pressure targeted ventilation decreased the occurrence of events (all P < 0.01). During volume controlled synchronized intermittent mandatory ventilation and pressure targeted ventilation, ventilator settings were associated with the incidence of overall PVA. The number of overall PVA, as well as double triggering and flow starvation specifically, were associated with worse outcomes and fewer hospital-free days (all P < 0.01). Double triggering and flow starvation are the most common PVA among critically ill, mechanically ventilated patients. Overall incidence as well as double triggering and flow starvation PVA specifically, portend worse outcome.

scholarly journals The lower respiratory tract microbiome of critically ill patients with COVID-19

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Paolo Gaibani ◽  
Elisa Viciani ◽  
Michele Bartoletti ◽  
Russell E. Lewis ◽  
Tommaso Tonetti ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Lower Respiratory Tract ◽  
Multidrug Resistant ◽  
Carbapenem Resistant ◽  
Lung Microbiome ◽  
Bacterial Microbiome ◽  
Unweighted Unifrac ◽  
Bacterial Superinfection

AbstractCOVID-19 infection may predispose to secondary bacterial infection which is associated with poor clinical outcome especially among critically ill patients. We aimed to characterize the lower respiratory tract bacterial microbiome of COVID-19 critically ill patients in comparison to COVID-19-negative patients. We performed a 16S rRNA profiling on bronchoalveolar lavage (BAL) samples collected between April and May 2020 from 24 COVID-19 critically ill subjects and 24 patients with non-COVID-19 pneumonia. Lung microbiome of critically ill patients with COVID-19 was characterized by a different bacterial diversity (PERMANOVA on weighted and unweighted UniFrac Pr(> F) = 0.001) compared to COVID-19-negative patients with pneumonia. Pseudomonas alcaligenes, Clostridium hiranonis, Acinetobacter schindleri, Sphingobacterium spp., Acinetobacter spp. and Enterobacteriaceae, characterized lung microbiome of COVID-19 critically ill patients (LDA score > 2), while COVID-19-negative patients showed a higher abundance of lung commensal bacteria (Haemophilus influenzae, Veillonella dispar, Granulicatella spp., Porphyromonas spp., and Streptococcus spp.). The incidence rate (IR) of infections during COVID-19 pandemic showed a significant increase of carbapenem-resistant Acinetobacter baumannii (CR-Ab) infection. In conclusion, SARS-CoV-2 infection and antibiotic pressure may predispose critically ill patients to bacterial superinfection due to opportunistic multidrug resistant pathogens.

The relationship between sedative drug utilization and outcomes in critically ill patients undergoing mechanical ventilation

2016 ◽  
Vol 30 (5) ◽  
pp. 763-769 ◽  
Author(s):  
Kenshi Hayashida ◽  
Takeshi Umegaki ◽  
Hiroshi Ikai ◽  
Genki Murakami ◽  
Masaji Nishimura ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Critically Ill ◽  
Drug Utilization ◽  
Critically Ill Patients ◽  
Sedative Drug ◽  
The Relationship

scholarly journals Neutrophil Gelatinase-Associated Lipocalin as a Marker for Renal Dysfunction Detection in Critically Ill Patients with Increased Intraabdominal Pressure

2017 ◽  
Vol 3 (1) ◽  
pp. 24-28
Author(s):  
Claudiu Puiac ◽  
Janos Szederjesi ◽  
Alexandra Lazăr ◽  
Codruța Bad ◽  
Lucian Pușcașiu
Keyword(s):  
Renal Function ◽  
Intensive Care ◽  
Creatinine Clearance ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Abdominal Cavity ◽  
Intraabdominal Pressure ◽  
Abdominal Pressure ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Neutrophil Gelatinase

Abstract Introduction: Elevated intraabdominal pressure (IAP) it is known to have an impact on renal function trough the pressure transmitted from the abdominal cavity to the vasculature responsible for the renal blood flow. Intraabdominal pressure is found to be frequent in intensive care patients and also to be a predictor of mortality. Intra-abdominal high pressure is an entity that can have serious impact on intensive care admitted patients, studies concluding that if this condition progresses to abdominal compartment syndrome mortality is as high as 80%. Aim: The aim of this study was to observe if a link between increased intraabdominal pressure and modification in renal function exists (NGAL, creatinine clearance). Material and Method: The study enrolled 30 critically ill patients admitted in the Intensive Care Unit of SCJU Tîrgu Mures between November 2015 and August 2016. The study enrolled adult, hemodynamically stable patients admitted in intensive critical care - defined by a normal blood pressure maintained without any vasopressor or inotropic support, invasive monitoring using PICCO device and abdominal pressure monitoring. Results: The patients were divided into two groups based on the intraabdominal pressure values: normal intraabdominal pressure group= 52 values and increased intraabdominal group= 35 values. We compared the groups in the light of NGAL values, 24 hours diuresis, GFR and creatinine clearance. The groups are significantly different when compared in the light of NGAL values and GFR values. We obtained a statistically significant correlation between NGAL value and 24 hour diuresis. No other significant correlations were encountered between the studied items. Conclusions: NGAL values are increased in patients with high intraabdominal pressure which may suggest its utility as a cut off marker for patients with increased intraabdominal pressure. There is a significant decreased GFR in patient with elevated intraabdominal pressure, observation which can help in early detection of renal injury in patients due to high intraabdominal pressure. No correlation was found between creatinine clearance and increased intraabdominal pressure.

Study on Phenotypic Detection of Carbapenemase Producing Enterobacteriaceae in MBS Hospital, Kota

2021 ◽  
Vol 10 (29) ◽  
pp. 2181-2185
Author(s):  
Pooja Jain ◽  
Naveen Saxena
Keyword(s):  
Critically Ill ◽  
Multi Drug Resistance ◽  
Environmental Cleaning ◽  
Beta Lactamases ◽  
Contact Precautions ◽  
Carbapenem Resistant ◽  
Surgical Ward ◽  
Study Results ◽  
Class B

BACKGROUND The Carbapenemase Resistant Enterobacteriaceae (CRE) are associated with high rates of morbidity and mortality particularly amongst critically ill patients. Hence rapid laboratory detection of CRE hospitalized patients is highly desirable. The vast majority of carbapenemases belong to three of the four known classes of beta lactamases namely Ambler class A, Ambler class B metallobetalactamases (MBL) and Ambler class Doxacillinases (OXAs). The purpose of this study was to determine the prevalence of carbapenemases producing Enterobacteriaceae in clinical isolates in MBS hospital, Kota. METHODS This study was conducted in the Department of Microbiology at MBS Hospital, Kota from June 2020 to December 2020. 68 non repeat isolates (MDR) that were resistant to imipenem (10 mg) according to CLSI breakpoint were included in the present study. RESULTS Out of 68 imipenem resistant Enterobacteriaceae, 52 were carbapenemase producing as detected by Modified Hodge Test. As per our study, the prevalence of carbapenemase producing Enterobacteriaceae was 20.8%. Most commonly seen in K. pneumoniae isolated from urine and swab of critically ill and debilitated patients of surgical ward. CONCLUSIONS Curbing irrational usage of antimicrobials in India is urgently required. Thus, aggressive infection control efforts have been effective at decreasing rates of infections with KPC-producing bacteria in intensive care units and long-term acute care hospitals. Bundled interventions including enhanced environmental cleaning, active surveillance culturing and contact precautions, as well as antimicrobial stewardship are important in controlling KPC-producing bacteria. KEY WORDS Multi Drug Resistance Enterobacteriaceae (MDRE), Klebsiella Producing Carbapenemase (KPC), Carbapenem Resistant Enterobacteriaceae (CRE), Metallo Beta Lactamase (MBL), Modified Hodge Test (MHT)

scholarly journals Influence of Mechanical Ventilation on the Pharmacokinetics of Vancomycin Administered by Continuous Infusion in Critically Ill Patients

2017 ◽  
Vol 61 (12) ◽  
Author(s):  
Susanna Edith Medellín-Garibay ◽  
Silvia Romano-Moreno ◽  
Pilar Tejedor-Prado ◽  
Noelia Rubio-Álvaro ◽  
Aida Rueda-Naharro ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Creatinine Clearance ◽  
Continuous Infusion ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Volume Of Distribution ◽  
Stochastic Simulations ◽  
Population Pharmacokinetic

ABSTRACT Pathophysiological changes involved in drug disposition in critically ill patients should be considered in order to optimize the dosing of vancomycin administered by continuous infusion, and certain strategies must be applied to reach therapeutic targets on the first day of treatment. The aim of this study was to develop a population pharmacokinetic model of vancomycin to determine clinical covariates, including mechanical ventilation, that influence the wide variability of this antimicrobial. Plasma vancomycin concentrations from 54 critically ill patients were analyzed simultaneously by a population pharmacokinetic approach. A nomogram for dosing recommendations was developed and was internally evaluated through stochastic simulations. The plasma vancomycin concentration-versus-time data were best described by a one-compartment open model with exponential interindividual variability associated with vancomycin clearance and the volume of distribution. Residual error followed a homoscedastic trend. Creatinine clearance and body weight significantly dropped the objective function value, showing their influence on vancomycin clearance and the volume of distribution, respectively. Characterization based on the presence of mechanical ventilation demonstrated a 20% decrease in vancomycin clearance. External validation (n = 18) was performed to evaluate the predictive ability of the model; median bias and precision values were 0.7 mg/liter (95% confidence interval [CI], −0.4, 1.7) and 5.9 mg/liter (95% CI, 5.4, 6.4), respectively. A population pharmacokinetic model was developed for the administration of vancomycin by continuous infusion to critically ill patients, demonstrating the influence of creatinine clearance and mechanical ventilation on vancomycin clearance, as well as the implications for targeting dosing rates to reach the therapeutic range (20 to 30 mg/liter).

Gender, degree of obesity, and discrepancy between urea and creatinine clearance in peritoneal dialysis.

1998 ◽  
Vol 9 (3) ◽  
pp. 497-499
Author(s):  
A H Tzamaloukas ◽  
D Malhotra ◽  
G H Murata
Keyword(s):  
Peritoneal Dialysis ◽  
Creatinine Clearance ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Ideal Weight ◽  
Clearance Studies ◽  
Obese Subjects ◽  
The Difference ◽  
The Relationship ◽  
Linear Manner ◽  
One Way Anova

The effect of gender and degree of obesity on the size indicators V, used to normalize urea clearance (Kt/Vur), and body surface area (BSA), used to normalize creatinine clearance (Ccr), in peritoneal dialysis was studied by: (1) mathematical comparison of the formulae used to estimate V (Watson and Hume) with the Dubois formula used to estimate BSA in peritoneal dialysis; and (2) comparison of percent deviation of BSA (delta BSA%) and V (delta V%) from ideal weight estimates in 933 clearance studies performed in actual patients (555 in men and 378 in women on continuous ambulatory peritoneal dialysis). V was estimated by the Watson formulae and BSA by the Dubois formula in these studies. delta BSA% and delta V% were stratified in 10% increments in deviation of body weight from ideal (delta W%) in these studies. Mathematically, the relationship between V and BSA is not linear. In the same subject, as obesity develops (delta W% increases) and BSA increases in a linear manner, V increases exponentially. In addition, there are substantial differences in the relationship between V and BSA caused by gender. For the same height and BSA, men have a larger V than women. In the clearance studies performed in actual continuous ambulatory peritoneal dialysis patients, the difference between delta V% and delta BSA% increased significantly (P < 0.0001) from the wasted to the obese subjects by one-way ANOVA in both men and women. Normalization of urea and creatinine clearances by different size indicators creates two types of mathematical distortion in the relationship between the two clearances. One distortion is caused by the degree of obesity. The second distortion is caused by gender. Use of the same size indicator to normalize both urea and creatinine clearances would eliminate these distortions.

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