meropenem and Burns

Clinical efficacy of Ronem preparation was studied in injured persons, suffering deep burns. High efficacy of the preparation in an acute period of the burn disease was established concerning the reduction in severity of the syndrome of systemic inflammatory answer clinical signs, the infection complications prophylaxis, microbal sensibilization lowering and preservation of natural detoxication systems on subcompensation level.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Burns; Female; Humans; Male; Meropenem; Middle Aged; Sepsis; Thienamycins; Trauma Severity Indices; Treatment Outcome; Young Adult

Severe burn injury involves widespread skin and tissue damage leading to systemic inflammation, hypermetabolism and multi-organ failure. The hypermetabolic phase of burn injury has been associated with increased systemic antibiotic clearance; however, critical illness in the absence of burn may also induce similar physiologic changes. Continuous renal replacement therapy (CRRT) is often implemented in critically ill patients and may also affect antibiotic clearance. Although the pharmacokinetics (PK) of meropenem has been described in both the burn and non-burn critically ill populations, direct comparative data is lacking.. For this study, we evaluated PK parameters of meropenem from 23 critically ill patients, burn or non-burn, treated with or without continuous veno-venous haemofiltration (CVVH) to determine the contribution of burn and CVVH to the variability of therapeutic meropenem levels.. A two-compartment model best described the data and revealed creatinine clearance (CrCl) and total burn surface area (TBSA) as significant covariates on clearance (CL) and peripheral volume of distribution (Vp), respectively. Of interest, non-burn patients on CVVH displayed an overall lower inherent CL as compared to burn patients on CVVH (6.43 vs. 12.85 L/h). Probability of target attainment (PTA) simulations revealed augmented renal clearance (ARC) may necessitate dose adjustments, but TBSA and CVVH would not.. We recommend a standard dose of 1000 mg every 8 hours; however, if ARC is suspected, or the severity of illness requires a more stringent therapeutic target, we recommend a loading dose of 1000-2000 mg infused over 30 minutes to 1 hour followed by continuous infusion (3000-6000 mg over 24 hours), or intermittent infusion of 2000 mg every 8 hours.

Topics: Anti-Bacterial Agents; Burns; Continuous Renal Replacement Therapy; Critical Illness; Humans; Meropenem; Renal Insufficiency

The aim of this prospective cohort study was to evaluate the therapeutic target attainment of 3-hour extended infusion of meropenem in patients with septic burns in the early and late periods of septic shock.. Meropenem serum levels were determined by liquid chromatography from blood samples collected within 48 hours (early period) of therapy and 10 to 14 days afterward (late period). Pharmacokinetic properties were investigated by noncompartmental analysis, and the therapeutic target was defined as 100% of the time above the MIC (100%fT> MIC).. Fifteen patients with 90 measured meropenem concentrations were included. Throughout the entire course of antimicrobial therapy, the therapeutic target was attained against gram-negative pathogens with an MIC ≤ 2 mg/L. Pathogens with intermediate susceptibility to meropenem were only covered in the early phase of therapy.. Higher-dose regimens or continuous infusions may be necessary to guarantee antimicrobial coverage of meropenem against less sensitive pathogens in patients with septic burns.

Topics: Anti-Bacterial Agents; Burns; Critical Illness; Humans; Infusions, Intravenous; Meropenem; Microbial Sensitivity Tests; Prospective Studies; Shock, Septic; Thienamycins

Burn patients have numerous risk factors for multidrug-resistant organisms (MDROs) and altered pharmacokinetics, which both independently increase the risk of treatment failure. Data on appropriate antimicrobial dosing are limited in this population and therapeutic drug monitoring (TDM) for beta-lactams is impractical at most facilities. Technology is available that can detect genetic markers of resistance, but they are not all encompassing, and often require specialized facilities that can detect less common genetic markers. Newer antimicrobials can help combat MDROs, but additional resistance patterns may evolve during treatment. Considering drug shortages and antimicrobial formularies, clinicians must remain vigilant when treating infections. This case report describes the development of resistance to ceftazidime-avibactam in a burn patient. The patient was a 54-year-old burn victim with a 58% total body surface area (TBSA) thermal burn who underwent multiple courses of antibiotics for various Pseudomonal infections. The initial Pseudomonal wound infection was sensitive to cefepime, aminoglycosides, and meropenem. A subsequent resistant pseudomonal pneumonia was treated with ceftazidime-avibactam 2.5 g every 6 hours due to the elevated MIC to cefepime (16 mcg/mL) and meropenem (>8 mcg/mL). Although the patient improved over 7 days, the patient again spiked fevers and had increased white blood counts (WBC). Repeat blood cultures demonstrated a multidrug-resistant (MDR) Pseudomonas with a minimum inhibitory concentration (MIC) to ceftazidime-avibactam of 16 mcg/mL, which is above the Clinical and Laboratory Standards Institute (CLSI) breakpoint of 8 mcg/mL. At first, resistance was thought to have occurred due to inadequate dosing, but genetic work demonstrated multiple genes encoding beta-lactamases.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; beta-Lactamases; Burns; Cefepime; Ceftazidime; Drug Combinations; Drug Resistance, Multiple, Bacterial; Genetic Markers; Humans; Meropenem; Microbial Sensitivity Tests; Middle Aged

Pseudomonas aeruginosa is a ubiquitous microorganism that is difficult to treat due to the increasing prevalence of multidrug resistance patterns. A total of 227 samples were taken from different clinical samples during the study period from January 2018 to December 2018. The isolates were identified with antibiotic sensitivity testing with ESBL by the Vitek-2 automated method. MDR, XDR, and PDR were determined. 40 (17.6%) isolates were positive for P. aeruginosa, maximum of ESBL and MBL. Positive isolates were detected in the burn, coexisting ESBL + MBL enzymes in 21 (52.5%) of our isolates. Imipenem followed by Meropenem were found to be effective against ESBL and MBL producers. Resistance was reached between 72-100% to 5 antibiotics. The frequency of PDR, MDR, and XDR were 5%, 50%, and 45%, respectively. The frequency of co-production between MDR, XDR, and PDR with MBL, ESBL, and Biofilm was 35%, 12.5% and 5%, respectively. Among the ESBLs, the frequency of distribution of bla VEB-1gene and blaGES-5 gene was 50% and 40 %, respectively. Bacterial isolates simultaneously carrying blaVEB-1 gene with multiple β-lactamases of different classes of biofilm, MDR, PDR, and XDR as same as a coexisting blaGES-5 gene. One isolate was detected as new isolates registered in global gene bank as locally P. aeruginosa isolates in Erbil city (LOCUS MN900953). The phylogenetic trees of the blaVEB gene isolates were demonstrated a genotype closely related to others, deposited in GenBank similar to the P. aeruginosa gene; gene sequencing revealed a 99% similarity with other isolates deposited in GenBank.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Base Sequence; beta-Lactamases; Biofilms; Burns; Drug Resistance, Multiple, Bacterial; Genotype; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Sequence Homology, Amino Acid

Acinetobacter baumannii (A. baumannii) is one of the leading pathogens in hospital infections. To characterize the epidemiology of A. baumannii in a burn ward, we collected all A. baumannii isolates though 18 months. Antibiotic susceptibility and antibiotic resistant genes were tested. Multilocus sequence typing (MLST) was further used to molecularly subtype these isolates. These isolates showed a severe multidrug resistant phenotype with 85% resistance to imipenem and meropenem. Along with the resistant phenotype, antibiotic resistant genes were widely found among these isolates. The prevalences of OXA23, AmpC, PER and VIM were 65.1%, 84%, 37.7% and 53%, respectively. Fifteen reported STs and sixteen novel STs were found in this study. ST368 (35%) was the dominant type, followed by ST195 (15%), ST191 (12%), ST369 (10%) and ST208 (10%). Majority (82.8%) of these isolates belong to clonal group 92, indicating the nosocomial spreading of A. baumannii. Further monitoring and control measures for A. baumannii spreading are necessary.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Burn Units; Burns; Cross Infection; Drug Resistance, Multiple, Bacterial; Humans; Imipenem; Meropenem; Molecular Epidemiology; Multilocus Sequence Typing; Thienamycins; Wound Infection

In critical burn patients, the pharmacokinetic parameters (absorption, distribution, metabolism, and excretion) of many classes of drugs, including antibiotics, are altered. The aim of this study was to compare 2 groups of burn patients undergoing treatment for health care-associated infections with and without therapeutic drug monitoring.. A retrospective analysis of a clinical intervention (ie, a before/after study) was conducted with patients with health care-associated pneumonia, burn infection, bloodstream infection, and urinary tract infection in the burn intensive care unit of a tertiary care hospital. The patients were divided into 2 groups: (1) those admitted from May 2005 to October 2008 who received conventional antimicrobial dose regimens; and (2) those admitted from November 2008 to June 2011 who received antibiotics (imipenem, meropenem, piperacillin, and vancomycin) with doses adjusted according to plasma monitoring and pharmacokinetic modeling. General characteristics of the groups were analyzed, as were clinical outcomes and 14-day and in-hospital mortality.. Sixty-three patients formed the conventional treatment group, and 77 comprised the monitored treatment group. The groups were homogeneous, median age was 31 years (range: 1-90) and 66% were male. Improvement occurred in 60% of the patients under monitored treatment (vs 52% with conventional treatment); 14-day mortality was 16% vs 14%; and the in-hospital mortality was similar between groups (39% vs 36%). In the final multivariate models, variables significantly associated with in-hospital mortality were total burn surface area ≥30%, older age, and male sex. Treatment group did not affect the prognosis.. Therapeutic drug monitoring of antimicrobial treatment did not alter the prognosis of these burn patients. More trials are needed to support the use of therapeutic drug monitoring to optimize treatment in burn patients.

Topics: Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Burns; Child; Child, Preschool; Cross Infection; Drug Monitoring; Female; Humans; Imipenem; Infant; Intensive Care Units; Male; Meropenem; Middle Aged; Piperacillin; Pneumonia; Prognosis; Tertiary Care Centers; Thienamycins; Urinary Tract Infections; Vancomycin; Young Adult

The wound healing process is frequently associated with a number of major clinical challenges, due to the failure of commonly used antibiotics as a remedy for wounds. There have always been fascinating questions about the novel applications of bioactive glasses (BGs) and it is expected that in the next few years these types of materials may play an important role in many aspects of soft tissue regeneration. This research focuses on the feasibility of using silver- and fluoride-containing BGs against multidrug-resistant bacterial strains isolated from patients with burns. According to the results obtained, fluoride did not exhibit antibacterial activity against the tested bacteria, while both 1% and 2% silver-containing BGs inhibited the bacterial growth. It is an important finding that 1% silver-containing BGs showed a potential antibacterial activity without any toxicity against fibroblasts, suggesting that this class of BGs could play a key role in the prevention of infection, reduction of pain, and removal of excessive exudates.

Topics: Amikacin; Animals; Anti-Bacterial Agents; Aztreonam; Burns; Carbenicillin; Cefepime; Ceftazidime; Ceftriaxone; Cell Survival; Cephalosporins; Ciprofloxacin; Drug Resistance, Multiple, Bacterial; Fluorides; Gentamicins; Glass; Humans; Imipenem; Meropenem; Mice; Microbial Sensitivity Tests; NIH 3T3 Cells; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Silver; Thienamycins; Tobramycin; Wound Infection

To develop a population model to describe the pharmacokinetics (PK) of intravenous meropenem in adult patients with severe burns and investigate potential relationships between dosage regimens and antimicrobial efficacy.. A dose of 1 g every 8 h was administered to adult patients with total body surface area burns of ≥15%. Doses for subsequent courses were determined using results from the initial course and the patient's clinical condition. Five plasma meropenem concentrations were typically measured over the dosage interval on one to four occasions. An open, two-compartment PK model was fitted to the meropenem concentrations using NONMEM and the effect of covariates on meropenem PK was investigated. Monte Carlo simulations investigated dosage regimens to achieve a target T>MIC for ≥40%, ≥60% or ≥80% of the dose interval.. Data comprised 113 meropenem concentration measurements from 20 dosage intervals in 12 patients. The parameters were CL (L/h) = 0.196 L/h/kg × [1 - 0.023 × (age - 46)] × [1 - 0.049 × (albumin - 15)], V1 = 0.273 L/kg × [1 - 0.049 × (albumin - 15)], Q = 0.199 L/h/kg and V2 = 0.309 L/kg × [1 - 0.049 × (albumin - 15)]. For a target of ≥80% T>MIC, the breakpoint was 8 mg/L for doses of 1 g every 4 h and 2 g every 8 h given over 3 h, but only 4 mg/L if given over 5 min.. Although 1 g 8 hourly should be effective against Escherichia coli and CoNS, higher doses, ideally with a longer infusion time, would be more appropriate for empirical therapy, mixed infections and bacteria with MIC values ≥4 mg/L.

Topics: Administration, Intravenous; Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Burns; Female; Humans; Male; Meropenem; Middle Aged; Monte Carlo Method; Plasma; Thienamycins; Time Factors

Adequate empirical antibiotic dose selection for critically ill burn patients is difficult due to extreme variability in drug pharmacokinetics. Therapeutic drug monitoring (TDM) may aid antibiotic prescription and implementation of initial empirical antimicrobial dosage recommendations. This study evaluated how gradual TDM introduction altered empirical dosages of meropenem and imipenem/cilastatin in our burn ICU.. Imipenem/cilastatin and meropenem use and daily empirical dosage at a five-bed burn ICU were analyzed retrospectively. Data for all burn admissions between 2001 and 2011 were extracted from the hospital's computerized information system. For each patient receiving a carbapenem, episodes of infection were reviewed and scored according to predefined criteria. Carbapenem trough serum levels were characterized. Prior to May 2007, TDM was available only by special request. Real-time carbapenem TDM was introduced in June 2007; it was initially available weekly and has been available 4 days a week since 2010.. Of 365 patients, 229 (63%) received antibiotics (109 received carbapenems). Of 23 TDM determinations for imipenem/cilastatin, none exceeded the predefined upper limit and 11 (47.8%) were insufficient; the number of TDM requests was correlated with daily dose (r=0.7). Similar numbers of inappropriate meropenem trough levels (30.4%) were below and above the upper limit. Real-time TDM introduction increased the empirical dose of imipenem/cilastatin, but not meropenem.. Real-time carbapenem TDM availability significantly altered the empirical daily dosage of imipenem/cilastatin at our burn ICU. Further studies are needed to evaluate the individual impact of TDM-based antibiotic adjustment on infection outcomes in these patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Body Surface Area; Burn Units; Burns; Carbapenems; Cilastatin; Cilastatin, Imipenem Drug Combination; Cohort Studies; Computer Systems; Critical Illness; Drug Combinations; Drug Monitoring; Female; Humans; Imipenem; Length of Stay; Male; Meropenem; Middle Aged; Retrospective Studies; Thienamycins; Young Adult

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Burns; Cefoperazone; Humans; Meropenem; Middle Aged; Minocycline; Retrospective Studies; Sulbactam; Thienamycins; Young Adult

To develop a population pharmacokinetic model of meropenem in burn patients and to explore the appropriateness of current dosage regimens.. Fifty-nine patients with burns ranging from 3% to 97% of total body surface area treated with meropenem were analysed. The population pharmacokinetic parameters of meropenem in 59 burn patients were estimated, and concentrations were simulated by using a mixed effect method (NONMEM, ver. 6.2).. The final model was a two-compartment model with first-order elimination where creatinine clearance (CL(CR)) and oedema contributed. The mean population pharmacokinetic parameters were clearance (L/h) =4.45 +10.5 × CL(CR) (mL/min)/138, V1 (central volume) =17.0+11.1 × presence of oedema (0 or 1) L, V2 (peripheral volume) =10.1 L and Q (intercompartmental clearance) =5.25 L/h with interindividual variability (CV%) of 31.5%, 44.4%, 67.2% and 0% (not estimated), respectively.. The population clearance and volume of distribution in our burn patients were significantly greater than those reported in non-burn patients. The simulation of 1000 virtual patients' plasma meropenem concentration treated with 1000 mg (30 min infusion) every 8 h based upon the model predicted the probability of achieving the time above MIC >40% of the dosing interval as 58.9% for Pseudomonas aeruginosa isolated from three university hospitals in Korea.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Burns; Female; Humans; Korea; Male; Meropenem; Metabolic Clearance Rate; Microbial Sensitivity Tests; Middle Aged; Pseudomonas aeruginosa; Thienamycins

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Body Surface Area; Burns; Erythrocyte Transfusion; Factor X Deficiency; Gastrointestinal Hemorrhage; Humans; Ibuprofen; Infant; Male; Meropenem; Shock; Thienamycins; Time

The pharmacokinetics of meropenem were investigated to examine its penetration into the skin of third degree burned rats. The rats were divided into two groups. One group acted as the control, and the other group had third degree burns induced by immersing their backs into 80 degrees C water for 20 seconds. The rats in each group were given 20 mg/kg of body weight of meropenem intravenously by one bolus injection seven days after burn inducement or depilation. In the non-burned control group, the maximum concentrations of meropenem in the serum and skin of 6.03 micrograms/ml and 0.12 microgram/g were respectively obtained 15 minutes after the injection and decreased very rapidly thereafter. In the burned rats, the maximum concentrations of meropenem in the serum, skin (eschar), and exudate fluid of 7.07 micrograms/ml, 1.44 micrograms/g and 5.99 micrograms/ml were respectively obtained 15 minutes after the injection and decreased very slowly. The penetration of meropenem into the burned skin was higher than that into the normal skin. These results suggest that meropenem is a very useful antibiotic in the treatment of burn infection.

Topics: Animals; Burns; Exudates and Transudates; Injections, Intravenous; Meropenem; Rats; Rats, Wistar; Skin; Thienamycins; Time Factors; Wound Infection