Version 9.0, Clinical characteristics and outcomes of Pseudomonas aeruginosa bacteremia in febrile neutropenic children and adolescents with the impact of antibiotic resistance: a retrospective study. For patients with suspected VAP or HAP, an empiric antimicrobial regimen that has activity against Staphylococcus aureus and Pseudomonas aeruginosa should be used. 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. Does NOT cover Pseudomonas aeruginosa or Acinetobacter. Beware significant rate of resistance of Pseudomonas in most institutions, so empiric double coverage often required. Moreover, for subjects weighing more than 50 kg, only 41.3% and 17% achieved these respective targets. 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. Notably, meropenem remains a viable option with efficacy against extended-spectrum beta-lactamase (ESBL)-producing organisms and Pseudomonas aeruginosa. 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. (1302 isolates) or sometimes meropenem discs were used (303 isolates in the years 2003–2006) to assess carbapenem susceptibility. A 3-h EI of meropenem 1000 mg Q8H achieved fT > 2 µg/mL > 40 on the first and third days, providing activity against sensitive strains of Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii. Ertapenem is a broad-spectrum carbapenem agent that lacks activity against Pseudomonas aeruginosa and has been available in Australia since 2002.1 Given the increasing prevalence of extended-spectrum β-lactamase (ESBL)-producing organisms and AmpC-producing Gram-negative bacteria, the use of carbapenems to treat non-P. aeruginosa infections is increasing.2 The use of the antipseudomonal carbapenems (aPCs), meropenem, doripenem and imipenem, in this situation may place ecological pres… © 2020 American Society for Clinical Pharmacology and Therapeutics. Of the 10 studies reviewed in depth, six were focused on premature and/or term newborns. The In vitro Activity of Meropenem to Nosocomial Pseudomonas aeruginosa Isolates. Precision of all parameter estimates was high and nonparametric bootstrap estimates were in close agreement with their parametric counterparts. with allergies to PCN who can’t take Pip/Tazo 3) Imipenem or Meropenem or Doripenem. The study of Smith et al.10 included 188 infants of 23–40 weeks estimated gestational age and 1–92 days postnatal age in whom 780 serum meropenem concentrations were obtained. or i.v. Anaerobic Coverage 1,2 All carbapenems have fairly good coverage against anaerobes. To begin, the model included both observed data from 188 subjects and simulated data from 100 subjects. 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. The approach of combining data from several PK studies on subpopulations may increase understanding of drug PKs in children. Detailed Meropenem dosage information for adults and children. Anahtar Kelimeler: Antibiyotik duyarlılığı, Meropenem, Pseudomonas aeruginosa. Options for covering both Pseudomonas and anaerobes: 1) Pip/Tazo (Zosyn), OR 2) Aztreonam + Metronizadole, OR——- This is on DRMC’s guidelines recommend this combination in pts. Includes dosages for Skin and Structure Infection, Intraabdominal Infection, Nosocomial Pneumonia and more; plus renal, liver and dialysis adjustments. 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 … The combined PK data set for this study, therefore, consisted of the merged data from 188 subjects in the Smith et al.10 study and the data from the 100 simulated subjects replicating those subjects studied by Du et al.,6 Blumer et al.,1 and Parker et al.9 Missing clinical data in the combined data set were imputed using the last value carried forward; except for missing gestational age for infants and children > 120 days of age, for which the gestational age of 40 weeks was imputed. Therefore, the studies of Blumer et al.,1 Parker et al.,9 and Du et al.6 were further analyzed for inclusion in our modeling. The FDA recommendations for treatment of serious, deep tissue infections with meropenem have been based on carefully performed PK analyses.1-3, 5 Nevertheless, these infections are still associated with significant morbidity and further improvements in treatment are needed.31-33. Please check your email for instructions on resetting your password. 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. Pharmacokinetics: i.m. Hi, man of 66 years old has Pseudomonas aeruginosa after being in hospital for more than 1 month for surgery after cerebral hemorrhage . Meropenem plasma concentration data following intravenous administration for the combined data set were analyzed using a nonlinear mixed effects modeling approach (Phoenix NLME). Imipenem is slightly less potent for P. aeruginosa, and ertapenem should not be used for P. aeruginosa because of poor activity. Antibiotics that cover the difficult to kill gram-positive bacteria 1998 Dec. 114(6):1594-8. . For the very resistant P. aeruginosa, doripenem and meropenem are highly potent because they require multiple drug resistance pathways. A 3-h EI of meropenem 1000 mg Q8H achieved fT > 2 µg/mL > 40 on the first and third days, providing activity against sensitive strains of Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii. It is routinely used for HAP/HCAP/VAP as double-coverage for Pseudomonas (note more frequent dosing for PNA – 400 mg IV q8 hours) 2. 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. 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). 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".]. The stepwise development of a new PopPK model for all pediatric subjects was conducted. Rarely, both were used (five isolates). Further investigation is needed to develop new dosing strategies in these patients. Meropenem exerts its bactericidal action by interfering with vital bacterial cell wall synthesis. ɣ, the Hill coefficient for the maturation equation for CL and CL2, as described in the. For targets of 4 mg/L, 80% or less for subjects achieved targets with each of the alternative regimens. {{}} This site uses cookies. Pseudomonas infection can be treated with a combination of an antipseudomonal beta-lactam (eg, penicillin or cephalosporin) and an aminoglycoside. Although doubling the currently recommended dosage administered every 8 hours in these older children would decrease the number of inadequately treated patients, achievement of > 90% target attainment when the target is 2 mg/L requires administering recommended dosages every 6 hours or extending infusion duration to 3 hours. 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. Data simulation was needed due to lack of access to data sets in children over 3 months and our objective was to develop a universal PopPK model that characterizes meropenem disposition in all pediatric patients. Goodness‐of‐fit plots and visual predictive checks all suggested a good fit of the model to the data. 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 wrote the manuscript. The percentage of subjects achieving a therapeutic target improved to over 85% in group 5 subjects (< 50 kg) with each of these alternative regimens for the potential target of 2 mg/L. Meropenem is a carbapenem that has an excellent activity against many gram-positive and gram-negative aerobic, facultative, and anaerobic bacteria. •Conclusion: A regimen of 500mg IV q6h is able to achieve a similar probability of target attainment with A two‐compartment model fit the data best with scaling model parameters by body weight. Uses: As a single agent therapy for the treatment of complicated intraabdominal infections (including appendicitis and peritonitis) due to viridans group streptococci, E coli, Klebsiella pneumoniae, P aeruginosa, B fragilis, B thetaiotaomicron, Peptostreptococcus species Usual Adult Dose for Meningitis The effect of Pseudomonas aeruginosa infection on clinical parameters in steady-state bronchiectasis. Meropenem (Merrem) is an injectable carbapenem and beta-lactam antibiotic that interferes with bacterial cell wall synthesis in sensitive organisms; Has activity versus a wide array of organisms, including multi-drug resistant Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae. In addition, the prediction‐corrected visual predictive check demonstrated that concentrations in our compiled data set (observed and simulated) were concordant with predicted concentrations (i.e., 89.7% were within the 90% prediction interval of 5–95 percentiles) indicating the appropriateness of the final model. 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. DOES NOT cover MRSA or VRE The group 2 carbapenems (imipenem, meropenem and, more recently, doripenem) have been a mainstay of treatment for patients with serious hospital infections caused by Pseudomonas aeruginosa, Enterobacteriaceae and other difficult-to-treat Gram-negative pathogens as well as mixed aerobic/anaerobic infections.