Colistin Therapy, Survival and Renal Replacement Therapy in Burn Patients: A 10-Year Single-Center Cohort Study.

Purpose: Colistin is still a therapeutic cornerstone against multidrug-resistant gram-negative bacteria (MDRGN), mostly when other antibiotics do not gain adequate activity on these strains. In the present study, we evaluated in a cohort of burn patients the relationship between colistin therapy, survival and requirement of renal replacement therapy (CRRT). Patients and Methods: Retrospective study of 133 burn patients treated with iv colistimethate sodium (loading dose 9.0 × 106 IU, maintenance dose 4.5 × 106 IU BID) and 35 treated with other antibiotics for MDRGN infection including Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae between January 2008 and December 2017. Multivariate analysis with logistic regression was used to determine the effect of the predictors such as age, total body surface area (TBSA), third-degree burn areas, Revised Baux score, Charlson comorbidity score, length of stay, colistin dose and duration of treatment, mechanical ventilation, and need of CRRT on in-hospital mortality. To investigate the relationship between colistin and renal function, we focused on survivor patients as the completion of the therapeutic course of colistin represented the basic requirement to analyze its impact on the kidney. Results: Out of 133 colistin- and 35 other antibiotics-treated patients, 83 (62.4%) and 31 (88.6%) survived, and 53 (39.8%) and 3 (9.7%) required CRRT, respectively. The severity of burns, as well as CRRT requirement and mortality, was significantly higher in colistin-treated patients than in other antibiotics-treated patients. Age and TBSA% were the significant predictors of mortality. Out of 83 colistin-treated survivors, 19 (22.9%) required CRRT (9 before and 10 after the start of colistin), and 64 (77.1%) had a normal renal function. No difference about the colistin dose and baseline characteristics, but the revised Baux score was found between the 9 patients requiring CRRT before the colistin course and the 10 patients after. Similarly, among the 64 patients not undergoing CRRT, no difference was found between the patients treated with the cumulative dose of colistin <99.0 × 106 IU (n = 33, median daily dose of 4.0 × 106 IU) and >99.0 × 106 IU (n = 31, median daily dose of 9.0 × 106 IU) about the baseline characteristics and the daily median plasma creatinine over 24 days of therapy. Conclusion: Colistin therapy was associated with more severe burns, mortality, and CRRT requirement. A short course therapy, at appropriate cumulative dosage, can lead to clinical success without a significant association with severe renal impairment.

Observed concentrations of amikacin and gentamycin in the setting of burn patients with gram-negative bacterial infections: Preliminary data from a prospective study.

AIM OF THE STUDY: Critically ill populations often have shown subtherapeutic aminoglycosides' concentrations mostly because of unavoidable changes in drug volume distribution and clearance. We present a real life prospective study evaluating plasma concentrations for once-daily dosing for amikacin and gentamycin among a population of severe burn adults. METHODS: We conducted a real life prospective study on the plasma observed concentrations of amikacin and gentamycin among severe burn patients, using aminoglycoside as combination therapy. Antibiotics were prescribed at the standard doses of 15-20mg/kg/day for amikacin and 3-5mg/kg/day for gentamycin. RESULTS: Eight patients (4 in amikacin and 4 in gentamycin groups, respectively) were enrolled in the study. All subjects were admitted for severe burns. The most common site of infection was bloodstream (5; 62.5%) and pneumonia (4; 50%). Pseudomonas aeruginosa, followed by Klebsiella pneumoniae and multi-drug resistant Acinetobacter baumannii were the most prevalent agents isolated. Amikacin and gentamycin never achieved the target peak concentration of 60mg/L and 30mg/L: in our study Cmax, for amikacin, was 33.1±15.6mg/L (SD), while for gentamycin was 14.3mg/L±9. Cmax and total body surface area have shown a strong negative correlation with borderline statistical significance (amikacin: ρ=0.922, P=0.078; gentamycin: ρ=0.937, P=0.063). At the standard dosage, the pharmacokinetic/pharmacodynamic (PK/PD) target of Cmax>8×highest MIC was reached for 8 (53.3%) out of 15 isolated pathogens. CONCLUSIONS: The present study found that, in a population of septic burn patients, standard doses of gentamycin and amikacin most often lead to plasma concentrations under the PK/PD target.

Epidemiology, prevalence and risk factors for infections in burn patients: results from a regional burn centre's analysis.

Burn patients are at high risk of infections due to severe impairment of immunity and loss of skin barrier function. We aimed to describe the epidemiology, incidence and risk factors for infection in a cohort of burns patients. Two hundred patients were retrospectively enrolled and subdivided into infected (N = 81) and uninfected groups (N = 119). The cumulative prevalence of infections was 27% on day 7 and 43.8% on day 28. Skin and soft tissue infections (32%) were the most frequent. Carbapenem-resistant Acinetobacter baumannii (28%), Pseudomonas aeruginosa (26%) and methicillin-resistant Staphylococcus aureus (25%) infections were most prevalent. An indwelling central venous catheter (CVC; sub-hazard ratio [SHR] 7.41, 95% confidence interval [CI] 3.78-14.62) and revised Baux score (RBS; SHR 2.08, 95% CI 0.98-4.42) were associated with higher incremental infection rate while surgical treatment resulted in a protective factor (SHR 0.45, 95% CI 0.29-0.75). RBS may be useful to stratify the infection risk: a strict collaboration between surgeons and infectious disease specialists is needed to implement source control and antimicrobial surveillance.

Pharmacokinetics of meropenem in burn patients with infections caused by Gram-negative bacteria: Are we getting close to the right treatment?

OBJECTIVES: Infections caused by multidrug-resistant Gram-negative bacteria are associated with high mortality. A relevant concern is the efficacy of antibiotic therapy in burn patients in whom pathophysiological changes strongly influence pharmacokinetic (PK) parameters. This study aimed to describe the PK parameters of meropenem in a population of burn patients. METHODS: Blood samples were collected immediately before and 2 h and 5 h after the start of intravenous drug administration. Plasma meropenem concentrations were determined using an ultra-performance liquid chromatography-photodiode array method. RESULTS: Seventeen burn patients were enrolled in the study. Thirteen patients (76%) were treated with meropenem for infections byPseudomonas aeruginosa or Acinetobacter baumannii isolated from blood or wounds. Mean Cmax, Cmin, AUC0-24, half-life, drug clearance and volume of distribution were 28.9 mg/L, 3.7 mg/L, 280.2 mg h/L, 2.0 h, 19.0 L/h and 44.4 L, respectively. Six patients (35%) achieved a Cmin ≥3.3 mg/L and seven patients (41%) achieved a Cmax ≥ 28.4 mg/L, whilst nine patients (53%) achieved an AUC0-24 of >226 mg h/L. Given a minimum inhibitory concentration (MIC) of 0.5 mg/L, all patients satisfied the target AUC/MIC of >125, but when the MIC rises to 2 mg/L (the ECOFF), only five patients reached the desired AUC/MIC. Regarding fT>MIC at an MIC of 2 mg/L with a 2-h infusion time, 13 patients (76%) achieved the PK target (>75%). CONCLUSION: These data suggest that a combined 2-h infusion with a higher dosage of meropenem, including a loading dose, may be successful to achieve effective PK parameters.

Coupled-plasma filtration and adsorption for severe burn patients with septic shock and acute kidney injury treated with renal replacement therapy.

BACKGROUND: Coupled-plasma filtration adsorption (CPFA) is a sorbent-based technology aimed at removing soluble mediators of septic shock. We present our experience on the use of CPFA in septic shock severe burn patients with acute kidney injury (AKI) needing renal replacement therapy (RRT) with the main goal to evaluate efficacy and safety of CPFA in this specific subset of septic shock patients. METHODS: In this observational study, we retrospectively reviewed the medical notes of all burn patients admitted to our adult Burn Center who received CPFA, as part of the septic shock treatment requiring RRT, between January 2001 and December 2017 (CPFA group). We compared CPFA group with all the burn patients admitted to our Center in the same period of time, with the same range of relevant clinical characteristics, who developed AKI and were treated with RRT, but not CPFA (control group). We collected demographic characteristics, burn size, Sequential Organ Assessment Failure (SOFA) score, microbiological data, and patient outcome, in terms of in-hospital mortality rate and the probability of survival calculated using the revised Baux score. We also collected data regarding CPFA safety (hemorrhagic episodes, catheter associated-complications, hypersensitivity reactions) and efficiency (number and duration of CPFA sessions, plasma treated amount, plasma processed dose). RESULTS: 39 severe burn patients were treated with CPFA (CPFA group) (mean age 46.0 years, range 40.0-56.0 years; mean burn size 48.0% TBSA, range 35.0-60.0% TBSA), and 87 patients treated with RRT, but not CPFA, who had similar clinical characteristics (control group). Observed mortality rate was 51.3% in the CPFA group and 77.1% in the control group (p 0.004). Regarding factors affecting survival in the CPFA group, SOFA score on the 1st day of CPFA resulted significant (OR 2.016, 95% CI, 1.221-3.326; p < 0.004) in the multivariate analysis logistic model. CONCLUSIONS: CPFA treatment for burn patients with AKI-RRT and septic shock, sustained by bacterial strains non or poorly responsive to therapy, was associated with a lower mortality rate, compared to RRT alone. However, further research, such as large prospective studies, is required to clarify the role of CPFA in the treatment of burns with septic shock and AKI-RRT.

Desórdenes conversivos en la niñez y adolescencia temprana / Conversive disorders of childhood and adolescence

Se realiza estudio descriptivo de los desórdenes conversivos en la niñez y adolescencia temprana. Se revisan fichas de 29 niños y adolescentes, 7 varones y 22 niñas hospitalizados entre los años 1982 y 1987 en el Servicio de Salud Mental Infantil del Hospital Roberto del Río. Se estudian diversas variables, como edad, sexo, tipo de síntomas, lapso entre inicio del síntoma y primera consulta, situación desencadenante, repercusión del síntoma, tiempo transcurrido desde la primera consulta a la desaparición del síntoma, sintomatologíaprevia, evolución post-alta, dificultades de rendimiento escolar, dinámica familiar. Se señala que en los síndromes conversivos hay un franco predominio de mujeres respecto a los varones y que en las formas mixtas son más frecuentes respecto a las manifestaciones motoras o sensoriales únicas. La causa desencadenante principal fue de índole relacional. La mayoría de los pacientes pertenecía a familias disfuncionales, siendo más frecuente la disfunción conyugal que la parental y esta disfunción se relacionaba con la iniciación, mantención y muy probablemente con la recaída de las manifestaciones clínicas. Se postula finalmente que el enfoque sistémico constituye una perspectiva promisoria en el estudio de los desórdenes conversivos