piperacillin--tazobactam-drug-combination and Burns

Patients with burn injuries are at high risk for infection as well as altered antimicrobial pharmacokinetics. Patients suffering from a burn injury, generally encompassing a total body surface area (TBSA) ≥ 20%, have been cited as at risk for augmented renal clearance (ARC). Our case report describes an obese patient with 3.2% TBSA partial thickness burns who suffered from burn wound cellulitis with Pseudomonas aeruginosa. Measured CLcr documented the presence of ARC, and 22.5 grams daily continuous infusion of piperacillin-tazobactam was initiated. Therapeutic monitoring of piperacillin at steady state was 78 mcg/mL, achieving the prespecified goal piperacillin concentration of 100% 4-times the minimum inhibitory concentration assuming MIC for susceptible P. aeruginosa at 16/4 mcg/mL per Clinical Laboratory Standards Institute. Available literature suggests younger critically ill patients with lower organ failure scores, and for a burn injury, a higher percentage of TBSA, are most likely to exhibit ARC which does not entirely align with the characteristics of our patient. In addition, piperacillin-tazobactam has been associated with altered pharmacokinetics in ARC, burn, and obese populations, demonstrating failure to meet target attainment with standard doses. We suggest a continuous infusion of piperacillin-tazobactam be used when ARC is identified. This case report describes the unique findings of ARC in a non-critically ill burn patient and rationalizes the need for further prospective research to classify incidence, risk factors, and appropriate antimicrobial regimens for burn patients with ARC.

Topics: Anti-Bacterial Agents; Burns; Critical Illness; Humans; Microbial Sensitivity Tests; Piperacillin; Piperacillin, Tazobactam Drug Combination; Tazobactam

Health care of severe burn patients is highly specialized and may require international patient transfer. Burn patients have an increased risk of developing infections. Patients that have been hospitalized in countries where carbapenemase-producing microorganisms (CPMO) are endemic may develop infections that are difficult to treat. In addition, there is a risk on outbreaks with CPMOs in burn centers. This study underlines that burn patients may extensively be colonized with CPMOs, and it provides best practice recommendations regarding clinical microbiology and infection control. We evaluated CPMO-carriage and wound colonization in a burn patient initially treated in Romania, and transported to the Netherlands. The sequence types and acquired beta-lactamase genes of highly-resistant microorganisms were derived from next generation sequencing data. Next, we searched literature for reports on CPMOs in burn patients. Five different carbapenemase-producing isolates were cultured: two unrelated OXA-48-producing Klebsiella pneumoniae isolates, OXA-23-producing Acinetobacter baumanii, OXA-48-producing Enterobacter cloacae, and NDM-1-producing Providencia stuartii. Also, multi-drug resistant Pseudomonas aeruginosa isolates were detected. Among the sampling sites, there was high variety in CPMOs. We found 46 reports on CPMOs in burn patients. We listed the epidemiology of CPMOs by country of initial treatment, and summarized recommendations for care of these patients based on these reports and our study.

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Burns; Colistin; Disasters; Enterobacter cloacae; Humans; Kanamycin; Klebsiella pneumoniae; Linezolid; Microbial Sensitivity Tests; Netherlands; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Providencia; Pseudomonas aeruginosa; Romania; Silver Sulfadiazine

Burn patients are prone to infections which often necessitate broad antibiotic coverage. Vancomycin is a common antibiotic after burn injury and is administered alone (V), or in combination with imipenem-cilastin (V/IC) or piperacillin-tazobactam (V/PT). Sparse reports indicate that the combination V/PT is associated with increased renal dysfunction. The purpose of this study was to evaluate the short-term impact of the three antibiotic administration types on renal dysfunction.. All pediatric and adult patients admitted to our centers between 2004 and 2016 with a burn injury were included in this retrospective review if they met the criteria of exposition to either V, V/IC, or V/PT for at least 48 h, had normal baseline creatinine, and no pre-existing renal dysfunction. Creatinine was monitored for 7 days after initial exposure; the absolute and relative increase was calculated, and patient renal outcomes were classified according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria depending on creatinine increases and estimated creatinine clearance. Secondary endpoints (demographic and clinical data, incidences of septicemia, and renal replacement therapy) were analyzed. Antibiotic doses were modeled in logistic and linear multivariable regression models to predict categorical KDIGO events and relative creatinine increase.. Out of 1449 patients who were screened, 718 met the inclusion criteria, 246 were adults, and 472 were children. Between the study cohorts V, V/IC, and V/PT, patient characteristics at admission were comparable. V/PT administration was associated with a statistically higher serum creatinine, and lower creatinine clearance compared to patients receiving V alone or V/IC in adults and children after burn injury. The incidence of KDIGO stages 1, 2, and 3 was higher after V/PT treatment. In children, the incidence of KDIGO stage 3 following administration of V/PT was greater than after V/IC. In adults, the incidence of renal replacement therapy was higher after V/PT compared with V or V/IC. Multivariate modeling demonstrated that V/PT is an independent predictor of renal dysfunction.. Co-administration of vancomycin and piperacillin-tazobactam is associated with increased renal dysfunction in pediatric and adult burn patients when compared to vancomycin alone or vancomycin plus imipenem-cilastin. The mechanism of this increased nephrotoxicity remains elusive and warrants further scientific evaluation.

Topics: Acute Kidney Injury; Adolescent; Adult; Analysis of Variance; Anti-Bacterial Agents; Burns; Child; Child, Preschool; Cilastatin; Cilastatin, Imipenem Drug Combination; Cohort Studies; Creatinine; Drug Combinations; Drug Therapy, Combination; Female; Humans; Imipenem; Incidence; Infections; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Texas; Vancomycin

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

Inhalation injury is suspected in patients with facial and neck burn-injuries and in patients who suffered burns in an enclosed space. Inhalation injury is associated with a disappointingly high morbidity and mortality in spite of advances in diagnostics and therapy.Prophylactic antibiotic therapy in patients with diagnosed inhalation injury is still a controversial subject.The epidemiologic characteristics of the burn patients with diagnosed inhalation injury in our clinic receiving prophylactic antibiotic therapy and mortality of these patients will be referred in this study.. Patients >16 years of age admitted to the burn unit between January 2008 and December 2012 and fulfilling the burn center referral criteria according the German Burn Association were enrolled in the study.. 58 patients (male:female 47:11) were diagnosed with an inhalation injury by their admission. The average length of hospital stay was 27.5 days, whereas of the patients with no inhalation injury was 16 days (p=0.04). 56.9% of the patients underwent tracheostomy. An escalation of the antibiotic therapy was done in 39.7% of the patients with inhalation injury and in 20.3% of the patients without one. The mortality of inhalation injury patients was 12.1%.. The development of pneumonia is not influenced in a statistical significant way by the use of prophylactic antibiotics. We do recommend the administration of prophylactic antibiotic therapy to patients with diagnosed inhalation trauma, as the mortality of these patients was lower in comparison to other studies.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Burn Units; Burns; Burns, Inhalation; Case-Control Studies; Female; Humans; Length of Stay; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Respiration, Artificial; Retrospective Studies; Tracheostomy; Young Adult

Piperacillin in combination with tazobactam, a β-lactamase inhibitor, is a commonly used intravenous antibiotic for the empirical treatment of infection in intensive care patients, including burn patients. The purpose of this study was to develop a population pharmacokinetic (PK) model for piperacillin in burn patients and to predict the probability of target attainment (PTA) using MICs and concentrations simulated from the PK model. Fifty burn patients treated with piperacillin-tazobactam were enrolled. Piperacillin-tazobactam was administered via infusion for approximately 30 min at a dose of 4.5 g (4 g piperacillin and 0.5 g tazobactam) every 8 h. Blood samples were collected just prior to and at 1, 2, 3, 4, and 6 h after the end of the infusion at steady state. The population PK model of piperacillin was developed using NONMEM. A two-compartment first-order elimination PK model was finally chosen. The covariates included were creatinine clearance (CLCR), day after burn injury (DAI), and sepsis. The final PK parameters were clearance (liters/h) (equal to 16.6 × [CLCR/132] + DAI × [-0.0874]), central volume (liters) (equal to 25.3 + 14.8 × sepsis [0 for the absence or 1 for the presence of sepsis]), peripheral volume (liters) (equal to 16.1), and intercompartmental clearance (liters/h) (equal to 0.636). The clearance and volume of piperacillin were higher than those reported in patients without burns, and the terminal half-life and PTA decreased with the increased CLCR. Our PK model suggests that higher daily doses or longer durations of infusion of piperacillin should be considered, especially for burn patients with a CLCR of ≥ 160 ml/min.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Burns; Computer Simulation; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Models, Statistical; Monte Carlo Method; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Young Adult

Burn patients are at high risk for nosocomial infections due to multiresistant bacteria, a large proportion of which are gram-negative. Tazobactam, a potent inhibitor of beta-lactamases, extends the spectrum of piperacillin to include many beta-lactamase producing bacteria. Consequently, it was decided to evaluate the activity of piperacillin/tazobactam in comparison with that of eight other antibiotics that are usually used for therapy against gram-negative bacterial infections in our burn unit. All consecutive gram-negative isolates from wounds, blood, respiratory tract, urine etc. from burn patients considered to be clinically significant were tested for their susceptibility to piperacillin/tazobactam, piperacillin, ceftazidime, cefotaxime, ceftriaxone, ciprofloxacin, gentamicin, amikacin and imipenem, determined by disk diffusion test. The zone inhibition was interpreted according to NCCLS recommendations. A total of 948 strains, isolated during the period of July, 1994 to September, 1995, made up of Pseudomonas spp (326), Acinetobacter spp (268) and Enterobacteriaceae (354), were tested. Overall piperacillin/tazobactam showed superior activity over the other antibiotics except for imipenem. Of the 948 isolates, 87% were susceptible to the combination, 56% to the three third generation cephalosporins, 69% to ciprofloxacin, 59% to the aminoglycosides and 97% to imipenem. Piperacillin/tazobactam showed strikingly superior activity over piperacillin alone against Acinetobacter spp followed by Enterobacteriaceae and the least against Pseudomonas. The emergence of Acinetobacter spp as a dominant gram-negative pathogen in burn patients and its high level of resistance against most of the antibiotics tested except piperacillin/tazobactam (87%) and imipenem (100%) were significant in light of the epidemiology of burn infections and treatment. This study suggests that piperacillin/tazobactam holds good promise against gram-negative infections in burn patients.

Topics: Burns; Cross Infection; Drug Therapy, Combination; Gram-Negative Bacteria; Humans; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination