cefepime and Burns

We studied the pharmacokinetics of cefepime (2 g bd) in six burns patients. Blood, urine and skin samples were collected to measure cefepime concentrations. A two-compartment model was fitted to the data. At day 1, t(1/2beta) was 2.45 +/- 0.56 h, V(ss) 0.36 +/- 0.1 L/kg, total clearance 152 +/- 25.2 mL/min, and AUC 217 +/- 34 mg*h/L. There was no statistical difference between day 1 and day 3 for any of the pharmacokinetic parameters. We demonstrated good penetration of cefepime in skin. These results show that it is not necessary to change the standard dosage of cefepime in burns patients.

Topics: Adult; Area Under Curve; Burns; Cefepime; Cephalosporins; Female; Half-Life; Humans; Injections, Intravenous; Male; Middle Aged

The pharmacokinetics of cefepime following administration of a single 2-g dose were evaluated for 12 adult patients with thermal burn injury and suspected or documented infection. Serial blood and urine samples for cefepime concentration determination were obtained for 24 h following drug administration. Serum and urine cefepime concentrations were determined by high-performance liquid chromatography and serum concentrations were fit to a two-compartment pharmacokinetic model. Mean (standard deviation [SD]) age, actual body weight (ABW), percent total body surface area burned, and days postburn at the time of study were 41 (13) years, 84 (22) kg, 36 (17)%, and 9 (3) days, respectively. Mean (SD) measured creatinine clearance (CL(CR)), total clearance (CL(T)), renal clearance (CL(R)), alpha phase half-life, beta phase half-life, and volume of distribution at steady state (V(SS)) were 135 (31) ml/min, 8.8 (2.4) liters/h, 8.1 (2.0) liters/h, 0.33 (0.14) h, 2.8 (0.6) h, and 0.43 (0.10) liters/kg ABW, respectively. Cefepime CL(T) and CL(R) in burn patients were similar to previously reported values for healthy volunteers when normalized by CL(CR). Stepwise multiple regression was used to associate CL(T) with CL(CR) and days postburn (r(2) = 0.861), CL(R) with CL(CR) and days postburn (r(2) = 0.773), nonrenal clearance with percent third-degree (% 3 degrees ) burn and albumin concentration (r(2) = 0.550), and V(SS) only with % 3 degrees burn (r(2) = 0.624). Simulated steady-state serum concentrations obtained by using the patients' pharmacokinetic parameters exceeded the susceptibility interpretive standard (breakpoint) of cefepime for at least 60% of the dosing interval with dosing regimens of 1 g every 8 h (q8h), 2 g q8h, and 2 g q12h. Despite differences in pharmacokinetic parameters between our patients and healthy volunteers, it appears that these dosing regimens may be adequate in similar burn patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Infections; Burns; Cefepime; Cephalosporins; Chromatography, High Pressure Liquid; Creatinine; Female; Half-Life; Humans; Male; Middle Aged; Spectrophotometry, Ultraviolet

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

An infectious wart of foot in a patient with diabetics is a medical challenge, and it gets worse when aggravated with burns. We present a case of a 67-year-old Pakistani man, diabetic for 20 years presented at our healthcare centre. While awaiting his culture sensitivity report, he was prescribed an empiric antibiotic therapy. Patient then travelled to Saudi Arabia for pilgrimage 3 days later with growth of

Topics: Aged; Anti-Bacterial Agents; Burns; Cefepime; Cephalosporins; Diabetes Mellitus, Type 2; Fluoroquinolones; Foot; Foot Diseases; Humans; Male; Moxifloxacin; Pakistan; Saudi Arabia; Staphylococcal Infections; Staphylococcus aureus; Warts

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

Multi-drug resistant P. aeruginosa has been increasing worldwide. Various mechanisms create this cross resistance in this bacterium including, acquisition beta-lactamases and intrinsic mechanisms, such as the presence of multidrug efflux pumps. Generally, multidrug efflux pumps inhibitor is used as a phenotypic method for the detection of active efflux pump systems.. In this study, 100 P. aeruginosa were collected from burn patients. Cefepime and imipenem resistant strains were isolated by disc diffusion agar and MIC. Carbonyl cyanide m-chlorophenyl hydrazone (CCCP), H+ conductor was used to detect activities of multidrug efflux pumps. The multidrug efflux genes of mexA, mexC and mexX were detected by PCR.. 87% and 79% of isolates were cefepime and imipenem resistant respectively. Only 18% of cefepime and imipenem resistant strains were inhibited by CCCP. 98% and 97% of isolates harbored mexA and mexC genes, respectively, while all of them harbored mexX.. Thus, cross resistance in P. aeruginosa isolates can be obtained by multidrug efflux pump systems. Therefore, the inhibition of multidrug efflux pumps can be very helpful for the treatment of infections caused by multi drug resistant P. aeruginosa.

Topics: Bacterial Outer Membrane Proteins; beta-Lactam Resistance; beta-Lactamases; Burns; Carbonyl Cyanide m-Chlorophenyl Hydrazone; Cefepime; Cephalosporins; Drug Resistance, Multiple, Bacterial; Genes, MDR; Humans; Imipenem; Iran; Membrane Transport Proteins; Microbial Sensitivity Tests; Phenotype; Polymerase Chain Reaction; Pseudomonas aeruginosa; Pseudomonas Infections

The patient is a 54-year-old man with severe thermal burn injury involving 45.5% of the total body-surface area, complicated with bacteremia caused by Pseudomonas aeruginosa with a cefepime MIC of 8 µg/ml. The plasma concentrations of cefepime 1 g every 6 h measured by validated high performance liquid chromatography were 25.8 µg/ml at 1 h and 6.28 µg/ml at 5 h after infusion, and 3.9 µg/ml before the infusion, when creatinine clearance was increased to 136 ml/min by vigorous fluid replacement. The pharmacokinetic-pharmacodynamic analyses in the one-compartment model with use of the Sawchuk-Zaske method revealed marked increase in the volume of distribution (28.9 l), total clearance (10.7 l/h), and shortening of plasma half- life (1.79 h) of cefepime, with time >MIC and 24-h area under the concentration-time-curve being 58% and 358, respectively. These pharmacokinetic parameters of cefepime quantified in the patient estimated a time >MIC of 87% if administered every 4 h. P. aeruginosa, however, was successfully eradicated without revision of the dosing regimen of cefepime. Decrease in creatinine clearance by correction of the fluid imbalance and wound closure by skin graft surgery likely contributed to the restoration of fluid shift, resulting in normal disposition of cefepime and favorable clinical outcome of the patient.

Topics: Anti-Bacterial Agents; Bacteremia; Burns; Cefepime; Cephalosporins; Humans; Male; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections

Three of seven clonally related Pseudomonas aeruginosa strains isolated from a burn patient produced the extended-spectrum beta-lactamase (ESBL) SHV-12. Its gene was flanked by two IS26 elements with a large transposon (>24 kb). The transposon also contained at least five IS26 elements and a gene encoding the amikacin resistance determinant aminoglycoside 6'-N-acetyltransferase type Ib [aac(6')-Ib]. It was inserted into the gene PA5317 in the P. aeruginosa chromosome.

Topics: Adult; beta-Lactamases; Burns; DNA Transposable Elements; Female; Humans; Microbial Sensitivity Tests; Polymerase Chain Reaction; Pseudomonas aeruginosa

The standard dosage recommendations for beta-lactam antibiotics can result in very low drug levels in intensive care (IC) patients and burn patients in the absence of renal dysfunction. We studied the pharmacokinetic parameters and serum concentrations of ceftazidime (CF) and cefepime (CE) in burn patients and analyzed the modifications according to clinical and biological parameters and in particular age and creatinine clearance.. Two pharmacokinetic studies were carried out with daily doses of 1 g x 6 for CF (n = 17) and 2 g x 3 for CE (n = 13). Creatinine clearance (CL(CR)) was both estimated and measured. Blood was sampled at steady state after an initial and a subsequent antibiotic dose. C(max) (maximal) and C(min) (minimal) concentrations were measured by HPLC. The influence of clinical and biological data was analyzed using ANOVA, ANCOVA and stepwise multiple linear regression.. The ratio of C(min) to the low MIC break point (4 mg/l) was lower than 4 in 52% of subjects receiving CF and in 80% of subjects receiving CE. The C(min) of CF was correlated with measured CL(CR) and was higher in mechanically ventilated patients than in non-ventilated patients. The clearance of CF was correlated with age. The C(min) of CE was correlated with age and drug clearance with measured CL(CR). Therefore dosage adjustment of these drugs in burn patients needs to take into account age, measured creatinine clearance and the danger of low concentrations occurring when the creatinine clearance is greater than 120 ml x min(-1).. In burn patients, the pharmacokinetic disposition of CF and CE was much more variable than in healthy subjects. Age and CL(CR) were predictors of the disposition of these antibiotics. Shortening the dosage interval or using continuous infusions will prevent low serum levels and keep trough levels above the MIC for longer periods of time. In view of the lack of a bedside measurement technique for ceftazidime and cefepime levels, we suggest a more frequent use of measured CL(CR) in order to attain efficacious clinical concentrations.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anti-Bacterial Agents; Burns; Cefepime; Ceftazidime; Cephalosporins; Chromatography, High Pressure Liquid; Creatinine; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Respiration, Artificial; Retrospective Studies

A liquid chromatographic method with UV detection for simultaneous determination of cefepime, vancomycin and imipenem has been developed. Cefuroxime was used as internal standard. After the clean up of samples by plasma protein precipitation, 5 microl of the extract were injected into the chromatograph and peaks were eluted from the Sulpelcosil LC-18 column using a mobile phase consisting of 0.075 M acetate buffer:acetonitrile (92:8, v/v), pH 5.0 at low rate (0.8 ml/min). The detection wavelength was 230 nm. The limit of detection was 0.4 microg/ml for cefepime and 0.2 microg/ml for vancomycin and imipenem. The method was applied to plasma samples of burn patients, and only small volumes of plasma were required for the simultaneous determination of those antimicrobial agents.

Topics: Adolescent; Anti-Bacterial Agents; Burns; Calibration; Cefepime; Cephalosporins; Chromatography, High Pressure Liquid; Drug Monitoring; Female; Humans; Imipenem; Male; Middle Aged; Reference Standards; Reproducibility of Results; Sensitivity and Specificity; Spectrophotometry, Ultraviolet; Vancomycin