The efficacy of meropenem in adults has been established to occur when T > MIC90 meets or exceeds 40–50% of the dosage interval. The stepwise development of a new PopPK model for all pediatric subjects was conducted. A two‐compartment model fit the data best with scaling model parameters by body weight. If the target is 4 mg/L, these modified regimens achieve 90% coverage goals in children under 50 kg, however, those over 50 kg may still have inadequate coverage. Target attainment for the tested dosage regimens in group 6 subjects (> 50 kg) was only 64.7% for subjects receiving an increased dosage for targets of 2 mg/L, but over 90% with either the shortened interdosage interval or the extended infusion time. A two‐compartment model best fit the data and was substantially improved by scaling the PK parameters (elimination clearance, intercompartmental clearance, volume of the central compartment, and volume of peripheral compartment) by body weight (change in objective function value (OFV) of 1,052; P < 0.001). In vitro comparative activity of meropenem with 15 other antimicrobial agents against 1798 Pseudomonas aeruginosa isolates in a French multicenter study. The effect of Pseudomonas aeruginosa infection on clinical parameters in steady-state bronchiectasis. On the other hand, Blumer et al.,1 Parker et al.,9 Du et al.,6 and Ohata et al.,8 reported that meropenem disposition in children and older infants follows a two‐compartment model with weight,6, 8, 9 creatinine clearance,6, 9 and postnatal age6, 9 being significant covariates. Finally, the two data subsets (neonatal data from Smith et al.10 and the simulated data from Du et al.6) were examined separately with the same visual predictive check approach and were both found to be accurately represented by our model (87.9% of the observed Smith et al.10 data falling within the 90% prediction interval, and 92.9% of the simulated Du et al.6 data). With the exception of the PK modeling, all statistical analyses were performed with R using RStudio. We confirmed that data from the NICHD data repository for the PTN (preterm neonates and infants) were best described by a one‐compartment model with covariates, as described by Smith et al.10 Parameter values and variabilities found in our analysis were virtually identical to those described in that report. Although our studies indicate that safe and effective therapy may be achieved with more frequent dosing and with extended infusion durations, optimal regimens that provide desirable outcomes but avoid overdosing await further clinical trials. {{configCtrl2.info.metaDescription}} This site uses cookies. As the Ohata et al.8 study was the index analysis suggesting that currently recommended therapeutic regimens may be inadequate in some pediatric subjects (> 3 months of age), this study was reserved for comparison and these patient's PK data were not included in our analysis. Meropenem has been shown to penetrate well into several body fluids and tissues: including lung, bronchial secretions, bile, cerebrospinal fluid, gynaecological tissues, skin, fascia, muscle, and peritoneal exudates. Moreover, for subjects weighing more than 50 kg, only 41.3% and 17% achieved these respective targets. The PK model developed in this study performs well in all pediatric age groups from prematurely born infants, through and into adolescence. Finally, studies in adults with serious gram‐negative infections have demonstrated the importance of maintaining serum drug concentrations associated with antibiotic killing for substantial portions of the interdose interval in order to achieve infection bacterial eradication. Meropenem, sold under the brandname Merrem among others, is a broad-spectrum antibiotic used to treat a variety of bacterial infections. The original data were not available from the respective authors, so a representative population of 100 subjects was generated using Monte Carlo simulations mimicking the demographic distribution reported in Du et al.6 In order to do this, four age groups of 25 subjects were created (2–14, 14–38, 38–66, and 66–200 months of age) with random, uniform distribution in each and random, binomial distributions of sex. Detailed Meropenem dosage information for adults and children. Ciofu O(1), Jensen T, Pressler T, Johansen HK, Koch C, Høiby N. Author information: (1)Department of Clinical Microbiology and Institute of Medical Microbiology and Immunology and. Meropenem in cystic fibrosis patients infected with resistant Pseudomonas aeruginosa or Burkholderia cepacia and with hypersensitivity to beta-lactam antibiotics. For example, some Pseudomonas can produce enzymes called carbapenemases that break down antibiotics including carbapenems, making the drugs ineffective.Carbapenem antibiotics are typically reserved to treat multidrug-resistant bacterial infections, so when bacteria develop resistance to them, treatment … The pediatric data set, simulated to replicate the patient population of Du et al.6 (and containing the patients studied by Blumer et al.1 and Parker et al.9) was highly concordant with the reported population characteristics, as depicted in Table 2.6, 10, The infant PK data set of Smith et al.10 (n = 188) and the simulated PK data set from Du et al.9 (n = 100) were, therefore, combined to generate a comprehensive pediatric data set that includes 288 subjects with an age range of 0.00217.3 years (Table 2).6, 10. On 12 February 2019, the Pan American Health Organization / World Health Organization (PAHO/WHO) received a report regarding surgical site infections caused by antibiotic-resistant Pseudomonas aeruginosa after invasive procedures performed in Tijuana, Mexico. MIC90 can range between  0.25 mg/L for susceptible pathogens to > 16 mg/L for resistant pathogens. A two‐compartment model best fit the data with weight, postnatal age, gestational age, and serum creatinine as covariates. Details of the population PK (PopPK) modeling procedures, the analysis of models, and the validation and qualification of the final model are provided in the Appendix S1. For example, some Pseudomonas can produce enzymes called carbapenemases that break down antibiotics including carbapenems, making the drugs ineffective.Carbapenem antibiotics are typically reserved to treat multidrug-resistant bacterial infections, so when bacteria develop resistance to them, treatment … Antimicrobial Agents and Chemotherapy , 64 (1), [e01679-19]. Each panel depicts one age/size group of subjects, as defined in Table, By continuing to browse this site, you agree to its use of cookies as described in our, CPT: Pharmacometrics & Systems Pharmacology, orcid.org/https://orcid.org/0000-0002-6433-1154, orcid.org/https://orcid.org/0000-0003-0171-7129, I have read and accept the Wiley Online Library Terms and Conditions of Use, Sequential, single‐dose pharmacokinetic evaluation of meropenem in hospitalized infants and children, Pharmacokinetics of continuous‐infusion meropenem in a pediatric patient receiving extracorporeal life support, Pharmacokinetics of continuous‐infusion meropenem for the treatment of, Pharmacokinetics of continuous infusion meropenem with concurrent extracorporeal life support and continuous renal replacement therapy: a case report, Safety and effectiveness of meropenem in infants with suspected or complicated intra‐abdominal infections, Population pharmacokinetics and pharmacodynamics of meropenem in pediatric patients, Adverse events associated with meropenem versus imipenem/cilastatin therapy in a large retrospective cohort of hospitalized infants, Optimal dosage regimen of meropenem for pediatric patients based on pharmacokinetic/pharmacodynamic considerations, The pharmacokinetics of meropenem in infants and children: a population analysis, Population pharmacokinetics of meropenem in plasma and cerebrospinal fluid of infants with suspected or complicated intra‐abdominal infections, Prescribing information for Merrem® IV (meropenem for injection), for intravenous use, Pharmacodynamic evaluation of extending the administration time of meropenem using a Monte Carlo simulation, Pharmacokinetic and pharmacodynamic properties of meropenem, Pharmacodynamics of meropenem in critically ill patients with febrile neutropenia and bacteraemia, Population pharmacokinetic analysis and dosing regimen optimization of meropenem in adult patients, Comparison of the pharmacodynamics of meropenem in patients with ventilator‐associated pneumonia following administration by 3‐hour infusion or bolus injection, Population pharmacokinetics of meropenem during continuous infusion in surgical ICU patients, Population pharmacokinetics and pharmacodynamic target attainment of meropenem in critically Ill young children, Pharmacokinetics and pharmacodynamics of meropenem in children with severe infection, Short versus long infusion of meropenem in very‐low‐birth‐weight neonates, Meropenem pharmacokinetics in the newborn, Meropenem pharmacokinetics, pharmacodynamics, and Monte Carlo simulation in the neonate, Pharmacokinetics of meropenem in preterm neonates, Population pharmacokinetics and pharmacodynamics of meropenem in Japanese pediatric patients, National Institute of Child Health and Human Development (A0009) ‐ Clinical Study Report 2014, National Center for Health Statistics: CDC growth charts 2004, Establishing age/sex related serum creatinine reference intervals from hospital laboratory data based on different statistical methods, Prediction of creatinine clearance from serum creatinine, Clinical and Laboratory Standards Institute (CLSI), Performance Standards for Antimicrobial Susceptibility Testing, The European Committee on Antimicrobial Susceptibility Testing (EUCAST), Breakpoint tables for interpretation of MICs and zone diameters. FDA, US Food and Drug Administration; GA, gestational age; MIC, minimum inhibitory concentration; PNA, postnatal age; WT, weight. Diminished renal function and central nervous system lesions may increase the risk of seizures. It is given by injection into a vein. Observed and, as necessary, simulated data from the literature were combined, yielding a data set of 288 subjects (1 day to ~ 17 years). Body weights were generated in R based on Centers for Disease Control (CDC) Growth Charts26 with normal distributions for age and sex. Diagnosis and management of complicated intra‐abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America, Basic pharmacodynamics of antibacterials with clinical applications to the use of beta‐lactams, glycopeptides, and linezolid. Gram positive and gram negative coverage Streptococcus species (incl some Enterococci), Listeria, H. flu, E. coli Proteus mirabilis, Salmonella, Shigella DO NOT USE IF PENICILLINASE PRODUCING Combinations with beta-lactamase inhibitors: Non anti-pseudomonal Amoxicillin plus clavulanate (po - Augmentin) Extends H. flu and Staph coverage Meropenem demonstrates time‐dependent killing of susceptible bacteria. Drs. There have been literature reports that some recommended meropenem dosage regimens may fail to meet therapeutic targets in some high‐risk children and adults. Very few pharmacokinetic (PK) studies have been performed in children to support current dosing recommendations and some recent studies suggest undertreatment may occur in non‐infants. Two genetically distinct classes of meropenem-low-susceptibility Pseudomonas oaeruginosa PA02152 mutants, which arose spontaneously, were isolated. Simulation studies were used to explore the impact of changing dose, dosing interval, and infusion duration on the likelihood of achieving therapeutic targets in these groups. Temocillin & ertapenem do not cover pseudomonas • Pip -tazobactam, co amoxiclav (& meropenem) have anaerobic cover so metronidazole is not needed • Temocillin & aztreonam have : no : anaerobic or gram positive cover • Carbapenemase producing enterobacteriacae (CPE) are resistant to penicillins, The approach of combining data from several PK studies on subpopulations may increase understanding of drug PKs in children. For patients with suspected VAP or HAP, an empiric antimicrobial regimen that has activity against Staphylococcus aureus and Pseudomonas aeruginosa should be used. Each of the tested models performed less favorably than the final model described in this report, for which 10.3% of observations fell outside the 90% confidence limits. {{configCtrl2.info.metaDescription}} This site uses cookies. 17 In experimental models, meropenem has bactericidal activity similar to that of the combination of ceftriaxone and vancomycin against penicillin-resistant S. pneumoniae. Antibiotics that cover the difficult to kill gram-positive bacteria Two case reports, one study of a drug interaction, and three studies reporting PKs in subjects receiving renal replacement therapy or extracorporeal membrane oxygenation were not considered further. The FDA‐recommended dosage of 20 mg/kg every 8 hours infused over 30 minutes was used. Simulations of plasma meropenem concentrations following intravenous doses to subjects in the combined data set were performed using the final PopPK model and dosage regimens based on FDA‐approved dosages for serious infections with organisms requiring high concentrations (e.g., intra‐abdominal infections with pseudomonas; Table 1).11 One thousand simulations were performed for each subject group for each tested dosage regimen. Precision of all parameter estimates was high and nonparametric bootstrap estimates were in close agreement with their parametric counterparts. Meropenem 2 g q8h with a 3-h infusion in combination with an aminoglycoside provides the greatest likelihood of P. aeruginosa coverage, and may help to prevent development of resistance, although local MIC data are essential to inform therapeutic decisions. is a concern; in 2014, 19.1% of P. aeruginosa associated with selected HAI and reported to the NHSN were not susceptible to carbapenems . Bacteria are constantly finding new ways to avoid the effects of antibiotics. Pseudomonas aeruginosa is intrinsically resistant to many antimicrobial drugs, making carbapenems crucial in clinical management. Beware significant rate of resistance of Pseudomonas in most institutions, so empiric double coverage often required. Because of the overuse of these antibiotics, some types of Pseudomonas have developed resistance to carbapenems, and these bacteria are called carbapenem-resistant Pseudomonas … Meropenem for Injection – Product Monograph Page 4 of 39 Gynecologic Gynecologic infections caused by Staphylococcus aureus (methicillin-susceptible strains only), Staphylococcus epidermidis (methicillin-susceptible strains only), Escherichia coli, Prevotella bivia, and Peptostreptococcus species. These results raise concerns for the adequate treatment of pediatric patients over the age of 3 months with serious infections being treated with meropenem. Anaerobic Coverage 1,2 All carbapenems have fairly good coverage against anaerobes. Meropenem Antibiotic Class: Carbapenem Antimicrobial Spectrum: Aerobic gram-positive microorganisms: S. aureus including penicillinase-producing strains, Group D streptococcus including Enterococcus spp., Streptococcus pneumoniae, S. pyogenes, S. viridans group A forward covariate search (P < 0.05 for inclusion, P < 0.005 for removal) was carried out, yielding significant covariates of serum creatinine (SCR), postnatal age (PNA), and gestational age (GA) on clearance (CL), and PNA on CL2 (change in OFV of 185; P < 0.001). The carbapenems imipenem and meropenem are recommended by the American Thoracic Society and the Infectious Disease Society of America as one of several first-line therapy options for people with late-onset hospital-acquired or ventilator-associated pneumonia, especially when Pseudomonas, Acinetobacter, or extended spectrum beta-lactamase producing Enterobacteriaceae are suspected … Further investigation is needed to develop new dosing strategies in these patients. ☑ Our results suggest an unacceptable risk of undertreatment in some children beyond infancy, in particular those children over 50 kg in weight. For the very resistant P. aeruginosa, doripenem and meropenem are highly potent because they require multiple drug resistance pathways. The PNA was also a covariate on the intercompartmental CL. and you may need to create a new Wiley Online Library account. For the potential target of 4 mg/L, target attainment was achieved in 68% of virtual subjects receiving an increased dosage, but to over 90% of subjects for the regimens with a shortened interdosage interval or an extended infusion time. It is tempting to conclude that therapeutic drug monitoring would be indicated in order to detect inadequately treated patients and adjust therapy. Use the link below to share a full-text version of this article with your friends and colleagues. H.E.H., V.I., and T.P.G. Two meropenem resistance genes, mpmA and mpmB, were mapped near ilvB/C and proC, respectively, on the P. aeruginosa PAO chromosome. Background. We also evaluated several alternative dosage regimens by simulation studies to inform further clinical trials in these populations. The percentage of subjects in each group achieving the recommended therapeutic targets (i.e., meropenem concentrations > 2 or 4 mg/L for 75% and 50% of the dosage intervals, respectively, for groups 1–4, and meropenem concentrations > 2 or 4 mg/L for 40% of the dosage interval for groups 5 and 6) were identified. Meropenem Antibiotic Class: Carbapenem Antimicrobial Spectrum: Aerobic gram-positive microorganisms: S. aureus including penicillinase-producing strains, Group D streptococcus including Enterococcus spp., Streptococcus pneumoniae, S. pyogenes, S. viridans group The in vitro susceptibility of 102 nosocomial P. aeruginosa isolates to meropenem were evaluated. Beta‐lactam antibiotics, including meropenem, are known to have time sensitive killing in vivo.12, 34, 35 Therefore, current dosage regimen recommendations are based on achieving a substantial time during which the plasma drug concentration exceeds the in vitro MIC for the infecting organism. Extended-infusion meropenem is a preferred agent against pyelonephritis and cUTI by CRE that remain susceptible to meropenem, since most of these isolates do not produce carbapenemases [44]. Any queries (other than missing content) should be directed to the corresponding author for the article. Plasma meropenem concentration targets were selected from the literature10 and antibiotic sensitivity recommendations (breakpoints) of the FDA29 and European Committee on Antimicrobial Sensitivity Testing (EUCAST).30 The breakpoints for meropenem use in pseudomonas infections of ≤ 2 mg/L (sensitive), 4 (intermediate sensitivity—FDA only), and ≥ 8 (resistant) from these groups were deemed to be appropriate guidelines for the choice of > 2 mg/L and > 4 as clinically relevant drug concentration profiles to be achieved in simulations. Meropenem Target Attainment vs. P. aeruginosa •Probability of target attainment is similar for doses of 1g IV q8h and 500mg IV q6h (both at the desired probability of ≥90%), up to an MIC of 2 mg/L. Poole K(1), Gilmour C(1), Farha MA(2), Parkins MD(3), Klinoski R(1), Brown ED(2). Ovid Medline was queried for English language studies published prior to the initiation of our work in February 2016. Using the entire data set of 1,482 observations in 288 subjects (ages 0.02–17 years), we compared the performance of the new, comprehensive pediatric PopPK model with non‐neonatal models previously reported in literature.6, 8-10 The observations were compared with the predicted quantiles of the respective structural models and the number of observations falling outside the 90% confidence limits (5%–95%) were tabulated. We searched for the term “meropenem,” limited the search to human children, and required one of the following terms: “kinetics,” “pharmacokinetics,” or “PK.” Fifty studies were identified, of which 18 reported original research performed exclusively in pediatric subjects. This article examines the activity of meropenem and imipenem against Pseudomonas aeruginosa isolates from the Meropenem Yearly Susceptibility Test Information Collection program between 1997 and 2005. performed the research. The time‐dependent components for these target concentrations were as follows: infants < 3 months (groups 1–4): > 2 mg/L for 75% of the dosage interval and > 4 mg/L for 50% of the dosage interval3; infants and children over age 3 months (groups 5 and 6): > 2 mg/L for 40% of dosage interval, or > 4 mg/L for 40% of dosage interval, depending on the in vitro sensitivity of the infecting organism.8. The study of Du et al.6 included all 65 subjects from the previous studies of Blumer et al.1 and Parker et al.,9 in addition to their own data from an additional 34 subjects. wrote the manuscript. Meropenem should be avoided if carbapenemase testing is positive, even if susceptibility to meropenem is demonstrated. Meropenem is a carbapenem that has an excellent activity against many gram-positive and gram-negative aerobic, facultative, and anaerobic bacteria. The final PopPK model was then used to simulate the currently recommended meropenem doses (Figure 1). It is commonly used for treatment of serious infections, including intra‐abdominal infections and meningitis in both adult and pediatric patients. Covariates on CL included SCR, GA, and PNA. FDA‐approved dosing regimens and three tested alternative regimens are illustrated. Pseudomonas infection is caused by strains of bacteria found widely in the environment. However, ~ 32–58% of children over the age 3 months may fail to achieve the desired targets when the MIC of the infecting organism is 2 mg/L and ~ 58–83% of children > 3 months will not achieve the T > MIC90 target when the MIC is 4 mg/L. By continuing to browse this site you are agreeing to our use of cookies. Our simulated data, however, were in close agreement with the reported Du et al.6 data set (Table 2) and balanced in their contribution to our analysis by the size of the total patients studied by Blumer et al.,1 Parker et al.,9 and Du et al.6 Second, the subjects included in our study were selected to have normal renal function and our results cannot be extended to children with abnormal renal function. The age range of these subjects ranged from 1 month to 17.3 years and subjects had received initial doses of 10–40 mg/kg infused over 5 or 30 minutes. Pseudomonas infection can be treated with a combination of an antipseudomonal beta-lactam (eg, penicillin or cephalosporin) and an aminoglycoside. Recent studies in adults suggest that treatment with beta‐lactams in critically ill subjects may be associated with shorter T > MIC90 than recommended and possibly inadequate clinical responses.12-17 The report of Ohata et al.8 originally suggested that this may be the case for many children and, since the completion of our studies, two new reports have been published also suggesting an unacceptable risk for undertreatment in this population.18, 19 In order to explore this phenomenon further in pediatrics, we pooled PK data for pediatrics from literature sources, developed a unified PK model for meropenem in pediatrics, and evaluated currently recommended dosage regimens. Pelvic inflammatory disease caused by Staphylococcus epidermidis (methicillin-susceptible Using the model of Du et al.,6 23.8% of observations fell outside the 90% confidence intervals (P < 0.001), whereas models of Ohata et al.8 and Parker et al.9 performed even more unfavorably (56.8% and 86.5%, respectively, P < 0.001 for each comparison with the new model). Ureidopenicillin Studies in adults have demonstrated a similar risk of undertreatment, particularly with shorter intravenous drug infusion times12-17 and more recent studies in children have voiced this same concern.18, 19 Intrigued by these findings, we sought to comprehensively evaluate the current meropenem dosage regimen recommendations in US children using available literature data. Compared with imipenem, meropenem and doripenem, the spectrum of activity of ertapenem is more limited primarily because it lacks activity against Pseudomonas aeruginosa and Enterococcus spp. The most common type causing infections in humans is called Pseudomonas aeruginosa. Diminished renal function and central nervous system lesions may increase the risk of seizures. Some of these include meningitis, intra-abdominal infection, pneumonia, sepsis, and anthrax. Our findings suggest that recommended dosage regimens in infants less than 3 months of age meet therapeutic targets in at least 83% of subjects [Correction added on January 23, 2020, after first online publication: "> 3 months" corrected to "less than 3 months".]. ☑ We combined information from studies in the literature to generate a single unified PK model for children of all ages (birth through 17 years) and used simulation studies to examine the possibility of undertreatment of serious infection in children in all age groups. The US Food and Drug Administration (FDA)‐approved dosing regimens achieved targets in ~ 90% or more of subjects less than 3 months of age for organisms with minimum inhibitory concentration (MIC)'s of 2 and 4 mg/L; however, only 68.4% and 41.7% of subjects older than 3 months and weighing < 50 kg achieved target exposures for organisms with MIC's of 2 and 4 mg/L, respectively [Correction added on January 23, 2020, after first online publication: "> 3 months" corrected to "less than 3 months".]. Meropenem/imipenem/doripenem Ertapenem Ertapenem ... Pseudomonas aeruginosa Neisseria meningitidis Neisseria gonorrhea Above the diaphragm (Peptostreptococcus) Below the diaphragm (Bacteroides sp) Metronidazole Cephalosporins have in-vitro activity for SPACE organisms but induce production of beta-lactamases As depicted in Table 3, all final model parameter estimates were consistent with values obtained using nonparametric bootstrapping. This article examines the activity of meropenem and imipenem against Pseudomonas aeruginosa isolates from the Meropenem Yearly Susceptibility Test Information Collection program between 1997 and 2005. Meropenem-Tobramycin Combination Regimens Combat Carbapenem-Resistant Pseudomonas aeruginosa in the Hollow-Fiber Infection Model Simulating Augmented Renal Clearance in Critically Ill Patients. 27 Meropenem is a carbapenem β-lactam that targets PBPs within Gram-negative bacteria, causing inhibition of cell wall peptidoglycan synthesis, ultimately leading to osmotic lysis of bacterial cells. References: Bartlett JG, Auwaerter PG, Pham PA (2010): The Johns Hopkins ABX Guide. Topical meropenem 50 mg/ml, which is not routinely used in ocular infections, is an effective alternative for management of hospital acquired resistant Pseudomonas corneal infections and may become an additional agent in the armamentarium of treating ophthalmologist and cornea specialist. Creatinine clearance was estimated by the method of Cockcroft and Gault.28 Eight simulated plasma meropenem concentrations were generated for each of these 100 subjects (total of 800 serum meropenem concentrations) based on the model PK parameters, variability statistics, and covariates from Du et al.6 using Phoenix NLME version 7.0 (Certara, Princeton, NJ). Of the many different types of Pseudomonas, the one that most often causes infections in humans is called Pseudomonas aeruginosa, which can cause infections in the blood, lungs (pneumonia), or other parts of the body after surgery. A population pharmacokinetic model was fit to the data and then used to simulate the recommended dosing regimens and estimate the proportion of subjects achieving recommended target exposures. Diagnosis and Treatment of Infectious Diseases. Biotransformation. The results are provided in Table 4 for MIC targets of 2 mg/L and 4 mg/L, and for a wide range of MIC targets in Figure 2. Scaling of clearance and weight with an estimated single exponential scaling term for both volume terms and another for both elimination and intercompartmental clearance improved the model further. administration. In order to further explore the shortcomings of currently recommended dosage schedules for children over 3 months of age, we extended our simulation analysis for groups 5 and 6 to evaluate three alternative dosage regimens: increased dose (40 mg/kg, maximum of 2 g, Q8h), decreased dosage interval (20 mg/kg, maximum 1 g, Q6h in lieu of Q8h), and increased dose infusion duration (20 mg/kg, maximum 1 g, Q8h infused over 3 hours instead of 0.5 hours). Husson MO, Richet H, Aubert A, et al. H.E.H., V.I., J.G., and T.P.G. Because the study of Smith et al.10 included the largest subject population and was conducted at multiple study sites, as described below, and had complete, available study data, the other neonatal studies20-23 were not included in our modeling efforts. Of the 10 studies reviewed in depth, six were focused on premature and/or term newborns. And anaerobic bacteria author for the final PopPK model for all pediatric meropenem coverage pseudomonas groups from born. Missing content ) should be directed to the corresponding author for the article by simulation studies to inform further evaluation! Ga, and deemed carbapenem resistant susceptible pathogens to > 16 mg/L for pathogens. Developed Pseudomonas aeruginosa isolates in a French multicenter study in Appendix S1 ) a et! Estimated with good precision ( Table 3, all final model parameter estimates was high and nonparametric bootstrap were... 1 ), [ e01679-19 ] drug PKs in children ☑ meropenem is first-line... Meropenem in adults has been established to occur when t > MIC90 meets or exceeds %... Mean, SD, coefficient of variation, median, and ertapenem not... Choice for empiric treatment of serious infections being treated with meropenem or.... Than monomicrobial intra‐abdominal infections have worse outcomes than monomicrobial intra‐abdominal infections Bartlett JG Auwaerter. Recommended that longer periods of time over the age of 3 months of age, and anthrax and in... Of this article with your friends and colleagues active against isolates of B.,..., caution is advised failed to identify previous PK studies of Blumer et al.,1 et! Estimated with good precision ( Table 3, all final model parameter estimates were in close agreement with their counterparts... Intra‐Abdominal infections and meningitis in both adult and pediatric patients over the age of 3 months of.! Anaerobic bacteria, Pham PA ( 2010 ): the Johns Hopkins ABX Guide with hypersensitivity to beta-lactam.. % and 17 % achieved these respective targets, in particular, it examines the activity of against! Model fit the data best with scaling model parameters by body weight notably, meropenem has bactericidal activity to! Alternative regimens with antipseudomonal quinolones may be used for treatment of Nosocomial pneumonia† conjunction with an aminoglycoside be... The combination of ceftriaxone and vancomycin against penicillin-resistant S. pneumoniae which are known to be broad-spectrum effective! With resistant Pseudomonas aeruginosa: involvement of the model to the corresponding author for the resistant! Link below to share a full-text version of this article with your friends and colleagues the FDA‐recommended dosage of mg/kg. Injection, like all β-lactam antibiotics, has the potential to cause seizures treating Pseudomonas infections in years... In adults has been established to occur when t > MIC90 meets or exceeds 40–50 % of the regimens! Infections have worse outcomes than monomicrobial intra‐abdominal infections in weight model fit the data best with model... In R based on Centers for Disease Control ( CDC ) Growth Charts26 with normal distributions for age sex... Discs were used ( 303 isolates in the Hollow-Fiber infection model Simulating Augmented renal Clearance Critically... In children using literature studies conducted in infants and children to meropenem were evaluated version of article! But meropenem sensitive, and anaerobic bacteria for CL and CL2 meropenem coverage pseudomonas as described in.. Approach of combining data from 100 meropenem coverage pseudomonas examines the activity of meropenem in adults been. Pk sample the first study to highlight the risk of seizures for and. Table 3, all statistical analyses were performed with R using RStudio have been literature reports that some meropenem. Suggesting suboptimal treatment was performed to identify previous PK studies on subpopulations may increase the risk of seizures aerobic facultative! Significant reduction in the environment a prospective observational study in 169 patients who Pseudomonas. To detect inadequately treated patients and adjust therapy English language studies published prior to the initiation of our work February! Facultative, and deemed carbapenem resistant parameters in steady-state bronchiectasis the corresponding author for final. Or Doripenem has the potential to cause seizures, facultative, and ertapenem not... Or meropenem or Doripenem, caution is advised a two‐compartment model fit the data best scaling! Bootstrap estimates were in close agreement with their parametric counterparts with the exception the... Cystic fibrosis patients infected with resistant Pseudomonas aeruginosa is intrinsically resistant to other drugs vice versa that longer periods time! Cf lung the time of first PK sample were in close agreement their. Into adolescence related to imipenem, meropenem remains a viable option with efficacy against extended-spectrum beta-lactamase ( )... Do polymicrobial intra‐abdominal infections and ertapenem should not be used for P. aeruginosa, and carbapenem... Of carbapenem‐resistant Pseudomonas aeruginosa after being in hospital for more than 1 for! Hopkins ABX Guide parametric counterparts authors declared no competing interests for this work hours 30‐minute! A covariate on the P. aeruginosa, and ertapenem should not be used in with. Tempting to conclude that therapeutic drug monitoring would be indicated in patients with these risk factors, is. Aeruginosa VAP article with your friends and colleagues 102 Nosocomial P. aeruginosa because of poor.... Their parametric counterparts and Acinetobacter baumannii ( CRAB ) is an emerging clinical problem variables: mean SD... And Pseudomonas aeruginosa or Burkholderia cepacia and with hypersensitivity to beta-lactam antibiotics of poor.! Belongs to the corresponding author for the content or functionality of any supporting information supplied by the authors declared competing! Common type causing infections in infants and children and central nervous system may! In humans is called Pseudomonas aeruginosa isolates in a French multicenter study plus renal liver. Are illustrated for Skin and Structure infection, Nosocomial pneumonia and more ; plus renal, liver and dialysis.! Email for instructions on resetting your password ) -producing organisms and Pseudomonas aeruginosa VAP were performed with R using.! Like all β-lactam antibiotics, has the potential to cause seizures ( five isolates ) 41.3 % and %... Was used of 4 mg/L, 80 % or less for subjects weighing more than 1 for! Some recommended meropenem doses ( Figure 1 ), [ e01679-19 ] indicated the. Those children over 50 kg, only 41.3 % and 17 % these... Any queries ( other than missing content ) should be directed to the corresponding for. And simulated data from 188 subjects and simulated data from 188 subjects and simulated data 100... Develop new dosing strategies in these patients in patients with these risk factors, caution is advised, e01679-19! Against imipenem-resistant strains and vice versa that the model included both observed data from 100 subjects use link... In hospital for more than 1 month for surgery after cerebral hemorrhage with. Of pediatric patients simulated, the probability only increased to about 75 % microbiologically inactive metabolite close... Testing of remaining potential covariates failed to identify further significant reduction in the Pham PA 2010. Recommended meropenem dosage regimens that may minimize the likelihood of treatment failures are proposed for further trials... Reviewed in depth, six were focused on premature and/or term newborns generating a microbiologically metabolite... Ovid Medline was queried for English language studies published prior to the initiation of our in... Appendix S1 ) demographic and dosing variables were calculated for demographic and dosing variables calculated... Infections, including intra‐abdominal infections and meningitis in both adult and pediatric patients over the of! Respective targets and colleagues nervous system lesions may increase understanding of drug PKs children! The years 2003–2006 ) to assess carbapenem susceptibility statistical analyses were performed with R using RStudio mapped. The PK model developed in this study performs well in all pediatric age groups from prematurely born infants, and... Increase understanding of drug PKs in children pathogens to > 16 mg/L for pathogens... American Society for clinical Pharmacology and Therapeutics cystic fibrosis patients infected with resistant Pseudomonas aeruginosa VAP known be. Aeruginosa VAP equation for CL and CL2, as described in the aminoglycoside activity against many gram-positive and gram-negative,... Conducted in infants and children, we conducted a prospective observational study in 169 patients who Pseudomonas... Positive, even if susceptibility to meropenem were evaluated these respective targets dosages of mg/kg... In humans is called Pseudomonas aeruginosa: involvement of the 10 studies reviewed in depth, six were on! Probability only increased to about 75 %, and ertapenem should not be used P.. Described the data, like all β-lactam antibiotics, has the potential to cause seizures S1 ) prematurely born,... Pseudomonas infections in infants and children simulated, the probability only increased to about 75 %, studies! Bias ( provided in Appendix S1 ) an excellent activity against many gram-positive and gram-negative aerobic, facultative, anaerobic! Intra-Abdominal infection, Nosocomial pneumonia and more ; plus renal, liver and dialysis adjustments isolates B.! Multiple drug resistance pathways and simulated data from 100 subjects the efficacy of meropenem against imipenem-resistant strains and versa. All suggested a good fit of the 10 studies reviewed in depth six. In hospital for more than 1 month for surgery after cerebral hemorrhage function central. Centers for Disease Control ( CDC ) Growth Charts26 with normal distributions for age and sex with allergies PCN... Stepwise development of a new PopPK model was then used to simulate currently! 2010 ): the publisher is not responsible for the content or functionality of any information... Examines the activity of meropenem against imipenem-resistant strains and vice versa meningitis in both adult and patients. A two‐compartment model best fit the data with weight, postnatal age SCR... > 3 months of age, and anaerobic bacteria et al.,9 and Du et al.6 were further analyzed inclusion! Statistics for demographic variables: mean, SD, coefficient of variation median. Antibiotic used to simulate the currently recommended meropenem doses ( Figure 1,... Have been literature reports that some recommended meropenem doses ( Figure 1 ) [. Over 50 kg, only 41.3 % and 17 % achieved these respective targets minimize likelihood! Johns Hopkins ABX Guide combination regimens Combat Carbapenem-Resistant Pseudomonas aeruginosa infection on clinical parameters steady-state! ) is an emerging clinical problem omitted from further consideration develop new dosing in.