BackgroundCases of ventilator-associated pneumonia (VAP) due to multidrug-resistant (MDR) gram-negative bacilli (GNB) mainly Acinetobacter baumannii, Pseudomonas aeruginosa and enterobacteria are common in hospitalised patients of Tunisian intensive care units (ICUs). Parenteral colistin has been used for the therapy of VAP caused by MDR GNB at Tunisian hospitals over the past few years with a favourable clinical response. However, its use fell out of favour because of the reported drug-related nephrotoxicity and neurotoxicity.ObjectivesTo determine whether aerosolised (AS) colistin was beneficial and safe in therapy of gram-negative VAP.MethodsThis was a randomised, single-blind study, in 149 critically ill adults who developed gram-negative VAP. Included patients were divided into two groups whether they received AS colistin (intervention group; n = 73) or intravenous (IV) colistin (control group; n = 76). AS colistin was given as 4 million units (MU) by nebulisation three times per 24 h. IV colistin was given as a loading dose of 9 MU followed by 4.5 MU two times per 24 h. Patients were followed during 28 days. Primary outcome was cure of VAP assessed at day 14 of therapy and defined as resolution of clinical signs of VAP and bacteriological eradication. Secondary outcomes were incidence of acute renal failure (ARF), mechanical ventilation length, ICU length of stay and 28-day mortality. Results were analysed based on intention-to-treat concept.ResultsThe patient’s baseline characteristics and distribution of pathogens VAP in both groups were similar. The clinical cure rate was 67.1 % in AS group and 72 % in IV group (p = 0.59). When administered in monotherapy or in combination, the AS regimen was as effective as IV regimen. Patients in AS group had significantly lower incidence of ARF (17.8 vs 39.4 %, p = 0.004), more favourable improvement of P/F ratio (349 vs 316 at day 14, p = 0.012), shortened time to bacterial eradication (TBE) (9.89 vs 11.26 days, p = 0.023) and earlier weaning from ventilator in ICU survivors with a mean gain in ventilator-free days of 5 days. No difference was shown in the length of stay and the 28-day mortality.ConclusionAerosolised colistin seems to be beneficial. It provided a therapeutic effectiveness non-inferior to parenteral colistin in therapy of MDR bacilli VAP with a lower nephrotoxicity, a better improvement of P/F ratio, a shortened bacterial eradication time and earlier weaning from ventilator in ICU survivors.Trial registration ClinicalTrials.gov Identifier: NCT02683603

Background: Colistimethate sodium (CMS) is the commercialized form of colistin that is effective against multiresistant Gram-negative bacilli. Its main side effects are nephrotoxicity and neurotoxicity. Pharmacodynamic dosages showed that they were infratherapeutic. Therefore, strategies with higher doses were proposed. The aim of this study was to assess the efficiency and toxicity of higher-dose CMS by comparing two treatment strategies: high-dose CMS versus standard-dose CMS. Methods: A prospective and comparative study of two matched groups was conducted. Fourty-six patients in each group were matched for age, severity and nature of infection. In the high-dose colistin group, CMS was administered at a loading dose of 9 MIU followed by a maintenance dose of 4.5 MIU/12 h. In the second group, retrospectively analyzed, colistin was administered at 6 MIU/day. For each group, clinical results, bacteriological eradication and daily creatinine clearance were recorded. Primary outcome measures were clinical cure defined as disappearance of infectious signs and eradication of microorganisms in all the follow-up cultures. Secondary outcome measures were incidence of acute renal failure and mortality. Results: Ninety-two patients were analyzed by matching. There was a higher cure rate in the high-dose group (63 vs. 41.3%, p = 0.04). No higher risk of nephrotoxicity was found by increasing daily doses of colistin (32.2 versus 26%, p = 0.64). Similarly, there was no significant difference in the time to onset of renal failure (8.32 vs. 11 days, p = 1) or in the requirement of hemodialysis (26.6 vs. 41%, p = 1). Conclusion: The high-dose colistin regimen is more efficient, without significant renal or neurological toxicity.

This paper demonstrates that the application of the MET model to the district general hospital improves the process of patient care. We are unable to conclude whether the MET alters morbidity or mortality for hospital inpatients.

Background: The kidney represents a potential target for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Acute kidney injury (AKI) can occur through several mechanisms and includes intrinsic tissue injury by direct viral invasion. Clinical data about the clinical course of AKI are lacking. We aimed to investigate the proportion, risk factors, and prognosis of AKI in critical patients affected with coronavirus disease 2019 (COVID-19).Methods: A case/control study conducted in two intensive care units of a tertiary teaching hospital from September to December 2020.Results: Among 109 patients, 75 were male (69%), and the median age was 64 years (interquartile range [IQR], 57–71 years); 48 (44%) developed AKI within 4 days (IQR, 1–9). Of these 48 patients, 11 (23%), 9 (19%), and 28 (58%) were classified as stage 1, 2, and 3, respectively. Eight patients received renal replacement therapy. AKI patients were older and had more frequent sepsis, acute respiratory distress syndrome, and rhabdomyolysis; higher initial urea and creatinine; more marked inflammatory syndrome and hematological disorders; and required more frequent mechanical ventilation and vasopressors. An elevated level of D-dimers (odds ratio [OR], 12.83; 95% confidence interval [CI], 1.9–85) was an independent factor of AKI. Sepsis was near to significance (OR, 5.22; 95% CI, 0.94–28; P=0.058). Renal recovery was identified in three patients. AKI, hypoxemia with the ratio of the arterial partial pressure of oxygen and the inspiratory concentration of oxygen <70, and vasopressors were identified as mortality factors.Conclusions: AKI occurred in almost half the patients with critical COVID-19. A high level of D-dimers and sepsis contributed significantly to its development. AKI significantly worsened the prognosis in these patients.

BackgroundEmpiric antimicrobial therapy (EAMT) using imipenem/colistin is commonly prescribed as a first line therapy in critically ill patients with severe sepsis. We aimed to assess the appropriateness of prescribing imipenem/colistin as EAMT in ICU patients.MethodsA 3-year observational prospective study included ICU patients that required imipenem/colistin as EAMT. The EAMT was assessed according to microbiological and clinical outcomes. The outcomes were: delay in apyrexia, delay in the decrease of the biological inflammatory parameters (BIP), the requirement for vasoactive agents, bacteriological eradication, length of stay, ventilator days and 30-day mortality.Results79 administrations of EAMT in 70 patients were studied. EAMT was appropriate in 52% of the studied cases. An ICU stay > 6 days was related to inappropriateness, and chronic respiratory failure was associated with appropriateness. In the appropriate EAMT group, we showed: earlier apyrexia, shorter delay in the decrease of the BIP and a reduced significant vasopressors requirement. Furthermore, EAMT improved survival with a median gain of 4 days. Inappropriate EAMT increased the mortality risk by six. The acquisition of NI in ICU was also an independent factor of mortality.ConclusionsEAMT using imipenem-colistin was appropriate in half of the cases and inappropriateness was associated with an increased ICU mortality risk.

Purpose To evaluate the effect of the positioning from the supine position (SP) to the prone position (PP) on the diaphragm activity in ventilated patients; using the ultrasound (US) imaging. Methods A cross-sectional comparative study before/after PP was conducted on 40 ICU patients over 18 years who received invasive ventilation (IV) for at least 48 h. The considered ventilator modes were: assisted control volume with a low trigger flow (between − 2 and 2 L/mn) and pressure support mode. US diaphragmatic assessments were performed at SP and at 60 min of PP. Both End-inspiratory and End-expiratory diameters (EID/EED) were taken at 3 levels of axillary lines and determined by the average values of multiple measures. Diaphragmatic thickening fraction (DTF) was calculated as: DTF = (EID − EED/EED) × 100. Pairing and ANOVA tests were used for comparisons. Results Forty ventilated patients (42 years of median age) at 4 days [2-7] of median duration of ventilation were examined during the two positions: SP versus PP. EID decreased from the SP to the PP (2.8 mm in SP vs. 2.4 mm in PP, p = 0.001). No difference was showed regarding the expiratory thickness. Overall, DTF didn't change in PP (37.4 vs. 42.05%, p = 0.36). When the patient was placed in PP, the best DTF value was showed at the posterior part of diaphragm (posterior: 45%, median: 31% and anterior: 38%, p = 0.049). Conclusion The ventral placement in ventilated patients reduced end-inspiratory diameter and tended to decrease DTF. In PP, the best contractile activity was detected at the posterior region of diaphragm.

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