Continuous infusion of cefiderocol in a critically ill patient with continuous venovenous haemofiltration.

Cefiderocol is a broad-spectrum cephalosporin antibiotic and is indicated in patients with difficult-to-treat Gram-negative bacterial infections. Cefiderocol is applied as a 2-4-times daily prolonged 3-h infusion. The therapeutic target of cefiderocol suggests that continuous infusion (CI) may be advantageous, since it is more likely to achieve 100% of time of the unbound concentration above the minimal inhibitory concentration (MIC). However, limited information on cefiderocol as CI has been assessed. We present a case of a critically ill 37-year-old woman with continuous venovenous haemofiltration (CVVH) treated with a CI of cefiderocol for multidrug-resistant Pseudomonas aeruginosa. She received 4 g per 24 h, in accordance with the recommendations for the total daily dose during CVVH with an effluent flow rate of 2.1-3 L/h. We evaluated intraperitoneal, plasma arterial pre- and postfilter and ultrafiltrate (urine) total cefiderocol concentrations and discussed the pharmacokinetics in respect to the CVVH settings. The predicted unbound plasma concentrations during CI resulted in 6.8-9.5-fold higher concentrations than the adopted MIC of 2 mg/L for cefiderocol against P. aeruginosa. The optimal time of the unbound concentration >MIC target of cefiderocol was met during the sampling period, suggesting adequate exposure during the total treatment period. The obtained intraperitoneal concentration indicated adequate cefiderocol exposure at the site of infection. Continuous infusion of 4 g cefiderocol per 24 h led to sufficient plasma concentrations in our anuric critically ill patient treated with CVVH. This case is supportive to the use of cefiderocol as continuous infusion.

Association of Baseline Renal Function with Mortality in Patients with Sepsis Requiring Continuous Renal Replacement Therapy for Acute Kidney Injury: A Single-Center Retrospective Study.

INTRODUCTION: To date, the prognosis of patients with sepsis and underlying chronic kidney disease (CKD) had been poor. However, the impact of preseptic renal function on the short-term prognosis of patients with extremely severe septic shock with acute kidney injury (AKI) that requires renal replacement therapy (RRT) is unclear. METHODS: Of the septic shock cases treated at the intensive care unit for ≥48 h, 131 adults who were diagnosed as septic AKI and underwent continuous venovenous hemodiafiltration were retrospectively analyzed. The relationships of demographic, clinical, and laboratory data with mortality were evaluated, and the independent risk factors for death were identified. RESULTS: The median age of the subjects was 73 (range, 63-80) years, and 76 (58%) were men. The rate of mortality was significantly higher among patients with CKD (n = 42) than in those without CKD (n = 89) (43% vs. 22%, p < 0.016). On univariate and multivariate logistic regression analyses, the associated factors and independent predictors of death were Sequential Organ Failure Assessment score (odds ratios [ORs] 1.151, 95% confidence intervals [CIs] 1.026-1.293, p = 0.017, and OR 1.129, 95% CI 1.003-1.271, respectively); baseline estimated glomerular filtration rate (OR 0.986, 95% CI 0.975-0.997, p = 0.016, and OR 0.983, 95% CI 0.970-0.996, respectively); and lactic acid (OR 1.094, 95% CI 1.005-1.190, p = 0.038, and OR 1.110 CI 1.015-1.215, respectively). CONCLUSION: Reduced baseline renal function may be a factor for poor short-term prognosis in severe septic AKI cases requiring RRT.

Therapeutic drug monitoring of antitubercular agents for disseminated Mycobacterium tuberculosis during intermittent haemodialysis and continuous venovenous haemofiltration.

WHAT IS KNOWN AND OBJECTIVE: There is a lack of data regarding therapeutic drug monitoring (TDM) of antitubercular agents in the setting of continuous venovenous haemofiltration (CVVH). We describe TDM results of numerous antitubercular agents in a critically ill patient during CVVH and haemodialysis. CASE SUMMARY: A 49-year-old man was initiated on treatment for disseminated Mycobacterium tuberculosis. During hospital admission, the patient developed critical illness and required renal replacement therapy. TDM results and pharmacokinetic calculations showed adequate serum concentrations of rifampin, ethambutol and amikacin during CVVH and of rifampin, pyrazinamide, ethambutol and levofloxacin during intermittent haemodialysis. WHAT IS NEW AND CONCLUSION: The presence of critical illness and renal replacement therapy can induce pharmacokinetic changes that may warrant vigilant TDM to ensure optimal therapy. To our knowledge, this is the first report to describe TDM for several antitubercular agents during CVVH in a critically patient with disseminated M. tuberculosis.

Efficacy of sustained low-efficiency dialysis in the management of topiramate intoxication: case report.

Guidelines on the use of dialysis treatment in patients with chronic kidney disease (CKD) and TPM (Topiramate) intoxication are controversial. A 51-year-old man with epilepsy and CKD was carried to our emergency department for dysuria and sickness. He chronically assumed TPM 100 mg 3/day. Creatinine level was 2.1 mg/dL, blood urea nitrogen 70 mg/dL, and inflammation indexes were increased. We started empirical antibiotic therapy and rehydration. The day two he had diarrhea and an acute insurgence of dizziness, confusion, and bicarbonate levels reduction. Brain CT resulted negative for acute events. During the night his mental status worsened, and urinary output results were about 200 mL in 12h. EEG showed desynchronized brain bioelectric activity. Thereafter, there was an episode of seizure and then anuria, hemodynamic instability, and loss of consciousness. Creatinine value was 5.39 mg/dL with a serious metabolic acidosis non-anion gap. We decided to start 6-hours Sustained Low Efficiency Hemo-Dia-Filtration (SLE-HDF). We assisted in the recovery of consciousness and later in the improvement of kidney function after 4 hours of treatment. TPM levels before SLE-HDF resulted in 123.1 µg/mL. At the end of treatment resulted in 30 µg/mL. To our knowledge, this is the first report of TPM involuntary intoxication in a patient affected by CKD who survived such a high TPM concentration treated with renal replacement therapy. SLE-HDF resulted in moderate elimination of TPM and acidemia resolution, continuous monitoring patient's vital parameters in relation to his hemodynamic instability, since blood flow and dialysate flow are lower than conventional hemodialysis.

Wasp stings and plasma exchange.

Invasive species related to climate change and/or globalization may be associated with novel forms of kidney disease. This is the case for wasps. Several species of Asian wasps are increasingly found in America (e.g. Asian giant hornet, Vespa mandarinia) and Europe (e.g. yellow-legged Asian hornet, V. velutina; black shield hornet, V. bicolor; and Oriental hornet, V. orientalis). Some of these species have been associated with human deaths and acute kidney injury. The literature on wasps and acute kidney injury is scarce and mostly originates from Asia, so nephrologists outside Asia are not familiar with this health problem. In a recent issue of ckj, Liu et al. describe a simple, four-item Wasp Sting Severity Score (WSS) developed from 1131 wasp sting patients. Vespa mandarinia and V. velutina were among those causing hospitalization, although most cases were caused by the black-bellied hornet (V. basalis). Liu et al. propose that a WSS ≥3 should guide early (<24 h after stings) plasma exchange, as plasma exchange was associated with lower mortality in severely affected patients but continuous venovenous haemofiltration and haemoperfusion were not. The WSS will require external validation. This manuscript should raise awareness about the potentially fatal consequences of stings by wasp species making their way into America and Europe.

Population pharmacokinetics of polymyxin B in critically ill patients receiving continuous venovenous haemofiltration.

Antibiotic dosing in critically ill patients undergoing continuous renal replacement therapy is considered challenging. This study aimed to analyse the population pharmacokinetics of polymyxin B in patients receiving continuous venovenous haemofiltration (CVVH), and to optimize individual dosing regimens in specific clinical scenarios. Patients treated with CVVH and polymyxin B for multi-drug-resistant Gram-negative bacterial infections were enrolled from two hospitals. Blood samples were collected during and outside CVVH, and assayed using a validated ultra-performance liquid chromatography-tandem mass spectrometry method. Population pharmacokinetic analysis and Monte Carlo simulations were performed using Phoenix NLME software. In total, 53 patients were included. The area under the concentration curve across 24 hours at steady state (AUCss,24h) of polymyxin B during CVVH was 27.94 ± 10.92 mg‧h/L, which was significantly lower than that outside CVVH (77.89 ± 35.66 mg‧h/L) (P=1.65 × 10-8). The population pharmacokinetic model revealed that CVVH significantly increased the clearance of polymyxin B. Monte Carlo simulations showed that for patients on CVVH, a loading dose of 200 mg plus a fixed maintenance dose of 150 mg every 12 h had a high probability of achieving AUCss,24h of 50-100 mg•h/L and the pharmacokinetic/pharmacodynamic target with a minimum inhibitory concentration ≤0.5 mg/L. For patients undergoing CVVH, high doses of polymyxin B and a dose-adjustment regimen based on therapeutic drug monitoring should be considered to improve efficacy.

Comparison of different modalities of continuous renal replacement therapy with regional sodium citrate anticoagulation in paediatric patients.

BACKGROUND: To evaluate the efficacy and safety of continuous renal replacement therapy (CRRT) modalities with regional sodium citrate anticoagulation (RCA) in children. METHODS: This retrospective study was conducted at the paediatric intensive care unit of Hunan Children's Hospital in China. Medical records of paediatric patients hospitalised for RCA-CRRT between April 2017 and March 2021 were reviewed. Patients received continuous venovenous haemodialysis, continuous venovenous haemofiltration (CVVH), or continuous venovenous haemodiafiltration (CVVHDF). RESULTS: Patients on continuous venovenous haemodialysis (n = 2) were excluded because of their small sample size. The remaining participants were divided into CVVH and CVVHDF groups; 80 patients received CRRT, with 40 and 62 sessions in the CVVH and CVVHDF groups, respectively. The filtre lifespan was longer in the CVVHDF group than in the CVVH group (median value [interquartile range]; 47 [15] hours vs. 35 [17.5] hours; p = 0.029). Compared with the CVVHDF group, the hazard ratio for filtre lifespan in the CVVH group was 3.023 (95% confidence interval 1.820-5.023, p < 0.001). There were no significant differences in ionised calcium levels of the circuits between the two groups at different time points (p < 0.05). Metabolic alkalosis, hyperlactataemia, hypocalcaemia, and hypercalcaemia occurred in both groups, with metabolic alkalosis being the most common complication. No patients in either group experienced sodium citrate accumulation or hypernatraemia. Inter-group differences in the incidence of these complications were not statistically significant (p > 0.05). CONCLUSIONS: Our results suggest that CVVHDF is a better option for RCA-CRRT than CVVH.

A 2-year-old boy with circulatory failure owing to streptococcal toxic shock syndrome: case report.

A 2-year-old boy presented with severe hypotension and acute kidney injury after a prodrome of non-bloody diarrhoea and fever in the preceding 3 days. He had a mild Ebstein cardiac anomaly but otherwise a normal past history and growth. On examination, he looked ill, his temperature was 37.5 °C, circulation was poor, and there were several purpuric lesions on the face, hands and scrotum. Haemoglobin was 7.8 g/dL (11-14), total white cell count 27 × 109/L, platelets 62 × 109/L, blood urea nitrogen 20.7 mmol/L (4.2-17.1), serum creatinine 95.4 µmol/L (21.2-36.2), CRP 154 mg/L (<5), AST 296 U/L (11-50), ALT 909 U/L (7-40) and C3 component of complement 0.8 g/L (0.9-1.8). Activated partial thromboplastin time (APTT) and prothrombin time (PT) were prolonged and fibrinogen level was 1.0 g/L (2-4). He received immediate fluid resuscitation (IV 0.9% saline solution, 2 × 10 ml/kg boluses, followed by glucose 5/0.45% sodium chloride solution, 2 × 10 ml/kg) and antibiotics (ciprofloxacin and amikacin) but circulation continued to deteriorate with development of decreased consciousness. He was placed on mechanical ventilation and vasopressor agents were added. Despite improved circulation over the next 2 days, he developed oliguria, progressive fluid overload, generalised oedema and a right-sided pleural effusion. Dialysis was commenced on day 3 of admission. Differential diagnosis included sepsis, atypical haemolytic uraemic syndrome and lupus nephritis. Blood and urine cultures remained negative but an anti-streptolysin O titre of 1318 (<200) IU/mL led to the diagnosis of streptococcal toxic shock syndrome which is rare in early childhood and associated with high mortality. Haemodialysis was commenced and continued for 10 days with successful treatment of fluid overload and subsequent extubation. Renal function was completely restored over the following 6 weeks and he was discharged in good clinical condition about 2 months after intial admission. The clinical course and outcome are discussed, and the importance of timely initiation of dialysis when there is fluid overload is emphasised.

Early haemoperfusion with continuous venovenous haemofiltration improves survival of acute paraquat-poisoned patients.

OBJECTIVE: To determine whether haemoperfusion (HP) with continuous venovenous haemofiltration (CVVH) improves the survival of patients with acute paraquat poisoning, compared with those treated using HP alone. METHODS: Medical records of patients with acute paraquat poisoning were analysed. Patients were randomised to undergo HP or HP + CVVH within 24 h of paraquat ingestion. Mortality rate, survival duration and cause of death were recorded. RESULTS: There were no significant differences in mortality rate between the HP group (n = 458) and the HP + CVVH group (n = 226) (57.4% and 58.4%, respectively). The mean survival duration was significantly longer in the HP + CVVH group than the HP group (8.6 ± 3.1 and 5.1 ± 2.3 days, respectively). Early circulatory collapse was a major cause of death in the HP group. The major cause of death in the HP + CVVH group was late respiratory failure. CONCLUSION: Combined therapy with HP and CVVH can prevent early death and prolong survival duration following acute paraquat poisoning, providing the opportunity for further treatment.