cilastatin--imipenem-drug-combination and Burns

In February 2018, one 54-year-old male patient with severe scald complicated with pneumonia and sepsis was transferred to Qingdao Municipal Hospital from other hospital. Drugs including cephalosporin, vancomycin, and imipenem/cilastatin combined with ciprofloxacin were used successively for anti-infective treatment, with no obvious effect. Multiple bacterial culture results of sputum, blood, and wound exudate showed infection of extensively drug resistant. 2018年2月，青岛市市立医院收治1例经外院转入的严重烫伤合并肺炎和脓毒症的54岁男性患者。先后使用头孢菌素、万古霉素、亚胺培南/西司他丁＋环丙沙星等抗感染治疗，但无明显效果。痰液、血液及创面分泌物多次细菌培养结果提示泛耐药铜绿假单胞菌感染。入院第4天调整抗感染治疗方案，补充血浆、红细胞及白蛋白，行营养支持及对症处理，同时进行用药监护，关注药物相关不良反应。经过10余天的治疗，患者感染得到有效控制，病情逐渐好转。本病例提示，严重烧伤患者易发生严重且致命的全身性感染，抗菌药物的不规范使用增加了泛耐药菌的感染风险，清晰的抗感染思路和抗菌药物的有效应用有助于提高感染治疗的成功率，对改善严重烧伤患者的预后具有重要价值。.

Topics: Anti-Bacterial Agents; Burns; Cilastatin, Imipenem Drug Combination; Humans; Male; Middle Aged; Pneumonia; Pseudomonas aeruginosa; Sepsis

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

To study the therapeutic effect of phages on extensively drug-resistant Acinetobacter baumannii-induced sepsis in mice.. (1) Sixty BALB/c mice were divided into blank control group, sepsis control group, antibiotics treatment group, phage treatment group, and phage control group according to the random number table, with 12 mice in each group. Mice in blank control group were intraperitoneally (the same injection position below) injected with 1 mL normal saline. Mice in sepsis control group, antibiotics treatment group, and phage treatment group were injected with 1 mL extensively drug-resistant Acinetobacter baumannii (the strain was isolated from the blood of a severely burned patient hospitalized in our unit) in the concentration of 5×10(7) colony-forming unit/mL to reproduce sepsis model. Two hours later, mice in sepsis control group, antibiotics treatment group, and phage treatment group were injected with 1 mL saline, 1 mg/mL imipenem/cilastatin, and 1×10(8) plaque-forming unit (PFU)/mL phages screened based on above-mentioned Acinetobacter baumannii (the same phages below) respectively. Mice in phage control group were injected with 1 mL phages in the titer of 1×10(8) PFU/mL. The injection was performed continuously for 7 days in each living mouse, and the survival situation of mice was observed each day to calculate the survival ratio in one week. (2) Another 60 BALB/c mice were grouped and treated as in experiment (1), and the injection was performed continuously for 5 days in each living mouse. On experiment day 2, 4, and 6, 3 mice from each group were selected (if the number of survived mouse in any group was less than 3 at sample collecting, all the survived mice were selected), and blood was drawn to determine white blood cell count (WBC, with 3 samples at each time point in each group). On experiment day 2, blood was drawn from the mice that had their blood taken earlier for bacterial culture, and lung, liver, kidney, and spleen tissue was collected from the same mice. The tissue samples were added to the LB solid medium after being homogenized and diluted for bacterial culture. The content of bacteria was calculated after the bacterial colony number was counted. Data were processed Wilcoxon rank sum test, one-way analysis of variance, LSD test and Kruskal-Wallis rank sum test.. (1) On experiment day 7, there were 12, 8, 10, and 12 mice survived in blank control group, antibiotics treatment group, phage treatment group, and phage control group respectively, while no mouse survived in sepsis control group. Compared with that in sepsis control group, the survival ratio of mice was significantly higher in the other four groups (with Z values from 55.635 to 106.593, P values below 0.05). The survival ratio of mice in phage treatment group was slightly higher than that in antibiotics treatment group, without statistically significant difference (Z=2.797, P>0.05). (2) On experiment day 2, WBC data of mice in blank control group, phage treatment group, and phage control group were close[respectively (5.60±0.94)×10(9)/L, (5.16±0.36)×10(9)/L, and (5.26±1.89)×10(9)/L], all significantly lower than the datum in sepsis control group[(8.64±0.64)×10(9)/L, P<0.05 or P<0.01], and the WBC data in the latter two groups were significantly lower than the datum in antibiotics treatment group[(7.80±1.76)×10(9)/L, with P values below 0.05]. On experiment day 4, WBC data of mice in antibiotics treatment group, phage treatment group, and phage control group were close, all significantly lower than the datum in blank control group (P<0.05 or P<0.01), and WBC data in the above-mentioned four groups were all lower than the datum in sepsis control group (with P values below 0.01). On experiment day 6, there was no statistically significant difference in WBC among blank control group, antibiotics treatment group, phage treatment group, and phage control group (χ(2)=4.128, P>0.05). On experiment day 2, respectively 12, 7, and 2 mice were detected as blood bacterial culture-positive in sepsis control group, antibiotics treatment group, and phage treatment group, while no positive result was detected in the other two groups. Positive ratios of blood bacterial culture of mice in blank control group, phage treatment group, phage control group were significantly lower than the ratio in sepsis control group (with χ(2) values from -30.000 to 30.000, P values below 0.01). Positive ratio of blood bacterial culture of mice in antibiotics treatment group was significantly higher than that in blank control group or phage control group (with χ(2) values respectively 17.500 and -17.500, P values below 0.05). On experiment day 2, except for the kidney tissue of mice in phage treatment group, the bacteria load in each viscus of mice in blank control group, phage treatment gro. Phages can significantly improve survival ratio, control inflammation response, and effectively clean bacteria in lung, liver, spleen, and kidney in treating extensively drug-resistant Acinetobacter baumannii-induced sepsis in mice.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacteriophages; Burns; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Resistance, Multiple, Bacterial; Humans; Imipenem; Liver; Mice; Mice, Inbred BALB C; Random Allocation; Sepsis; Soft Tissue Infections; Stem Cells

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

To investigate the pharmacokinetic characteristics of Imipenem/cilastatin in burn patients during the acute phase.. Imipenem concentrations in the plasma, blister and, interstitial fluids and urine of 6 burn patients (P group) were determined during the acute phase by high performance liquid chromatography after the first initial dose. Pharmacokinetic parameters were thus produced and statistically analyzed by program package STAT 5. Ten healthy volunteers served as control group (C group).. Compared to those in control group, pharmacokinetic parameters of Imipenem exhibited evident difference, such as prolonged half-life [(1.56 plus minus 0.55) h vs (1.06 plus minus 0.24) h] and enlarged distributing volume (16.16 plus minus 4.26) vs (13.96 plus minus 7.10). Imipenem could be detected in the blister and interstitial fluids of burn patients 1 hr after the initial dose. Renal clearance of Imipenem was positively correlated to creatinine clearance (r = 0.5834).. The intervals between doses should better be prolonged when loaded-dosage of Imipenem was administered in burn patients during the acute phase. Imipenem could penetrate II and III degree burn wound when given in the acute phase. Attention should be paid to renal function when Imipenem was given.

Topics: Adult; Burns; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Humans; Imipenem; Kidney; Male; Metabolic Clearance Rate