Severe mold fungal infections in critically ill patients with COVID-19.

The SARS-CoV-2 pandemic put an unprecedented strain on modern societies and healthcare systems. A significantly higher incidence of invasive fungal co-infections was noted compared with the pre-COVID-19 era, adding new diagnostic and therapeutic challenges in the critical care setting. In the current narrative review, we focus on invasive mold infections caused by Aspergillus and Mucor species in critically ill COVID-19 patients. We discuss up-to-date information on the incidence, pathogenesis, diagnosis and treatment of these mold-COVID-19 co-infections, as well as recommendations on preventive and prophylactic interventions. Traditional risk factors were often not recognized in COVID-19-associated aspergillosis and mucormycosis, highlighting the role of other determinant risk factors. The associated patient outcomes were worse compared with COVID-19 patients without mold co-infection.

Individualized digitally designed surgical template for guided soft tissue surgery in cases with severe gingival enlargement: A clinical application in hereditary gingival fibromatosis.

AIM: The purpose of this study was to present the use of computer-assisted periodontal surgery utilizing a novel surgical guide for cases with severe gingival enlargement through a clinical application in a patient with hereditary gingival fibromatosis. MATERIALS AND METHODS: The treatment plan included nonsurgical periodontal therapy, surgical periodontal treatment, and regular periodontal maintenance before the initiation of orthodontic treatment. Due to the increased soft tissue thickness, a surgical guide with a novel design was fabricated to facilitate the periodontal surgery since most of the patient's teeth were malpositioned and underexposed due to fibromatosis. For this purpose, the patient's intraoral scan was merged with a CBCT image in order to plan surgical excisions based on the anatomy of the teeth and the bone contour. RESULTS: The customized surgical guide facilitated the gingivectomy by controlling not only the shape of the initial incisions but also their orientation toward the level of the cementoenamel junction, improving the efficiency of the clinical time compared with freehand surgery and assisting in the verification of the final soft tissue shape, based on the treatment plan. CONCLUSION: Digital technology through the superimposition of multiple data sets can assist in the diagnosis and multidisciplinary management of cases with gingival fibromatosis. The proposed design of the surgical guide can facilitate soft tissue surgery based on the digital treatment plan, leading to more predictable management of the soft tissue, especially in patients with severe gingival enlargement, as in cases with hereditary gingival fibromatosis or drug-induced gingival overgrowth.

Severe Candida infections in critically ill patients with COVID-19.

The frequency of co-infections with bacterial or fungal pathogens has constantly increased among critically ill patients with coronavirus disease 2019 (COVID-19) during the pandemic. Candidemia was the most frequently reported invasive fungal co-infection. The onset of candidemia in COVID-19 patients was often delayed compared to non-COVID-19 patients. Additionally, Candida invasive infections in COVID-19 patients were more often linked to invasive procedures (e.g., invasive mechanical ventilation or renal replacement therapy) during the intensive care stay and the severity of illness rather than more "classic" risk factors present in patients without COVID-19 (e.g., underlying diseases and prior hospitalization). Moreover, apart from the increased incidence of candidemia during the pandemic, a worrying rise in fluconazole-resistant strains was reported, including a rise in the multidrug-resistant Candida auris. Regarding outcomes, the development of invasive Candida co-infection had a negative impact, increasing morbidity and mortality compared to non-co-infected COVID-19 patients. In this narrative review, we present and critically discuss information on the diagnosis and management of invasive fungal infections caused by Candida spp. in critically ill COVID-19 patients.

Systemic inflammatory markers following adjunctive Nd:YAG (1064 nm) laser irradiation to step 2 of periodontal therapy: a 12-month, randomized, controlled trial.

OBJECTIVES: The aim of this study was to investigate whether the use of adjunctive Nd:YAG (1064 nm) laser irradiation to full-mouth scaling and root planing (FM-SRP) may offer additional benefit in the systemic inflammatory status of the patient, as depicted in a variety of systemic biomarkers over FM-SRP alone, up to 12 months after treatment. MATERIALS AND METHODS: A total of 60 otherwise healthy stage III/IV periodontal patients were equally distributed in 3 groups. The control group received FM-SRP. In laser A group, 1 week after FM-SRP, Nd:YAG laser irradiation was delivered in periodontal pockets with PD ≥ 4 mm using specific settings (3 W, 150 mJ, 20 Hz, 100 µs). In laser B group Nd:YAG laser irradiation was delivered twice, 1 week after FM-SRP and 1 week later with different settings compared to laser A (2 W, 200 mJ, 10 Hz, 100 µs). RESULTS: A significant reduction (p = 0.038) of IL-1ß serum levels at the 6-month time point was observed for laser A group. IL-6 was found statistically significantly increased (p = 0.011) in the control group at the 6-week time point, whereas no difference was reported for the laser-treated groups (laser A, laser B). CONCLUSIONS: The adjunctive use of Nd:YAG laser irradiation, prevented from IL-6 increase after FM-SRP, 6 weeks after treatment. Similarly, Nd:YAG laser irradiation (3 W, 150 mJ, 20 Hz,100 µs) was associated with significantly lower IL-1ß levels, 6 months post-operatively. CLINICAL RELEVANCE: Additional Nd:YAG laser application to FM-SRP may provide a potential beneficial effect on systemic inflammation. TRIAL REGISTRATION NUMBER: ISRCTN26692900. REGISTRATION DATE: 09/06/2022.

Adjunctive Nd:YAG laser irradiation in the treatment of stage III/IV periodontitis: a 12-month, randomized, controlled trial.

OBJECTIVES: The aim of this study was to evaluate the clinical efficacy of the adjunctive use of Nd:YAG laser (1064 nm) to full-mouth scaling and root planning (FMS), in stage III/IV periodontitis patients. MATERIALS AND METHODS: Sixty stage III/IV periodontitis patients were randomly assigned to three groups. The control group received FMS, laser 1 group received combined FMS/single Nd:YAG laser irradiation (3 W, 150 mJ, 20 Hz,100 µs), and laser 2 group received combined FMS/double Nd:YAG laser irradiation with 1-week interval (2.0 W, 200 mJ, 10 Hz, 100 µs). PD, CAL, FMPS, GI, FMBS, and GR were evaluated at baseline, 6 weeks, 3, 6, and 12 months after treatment. Patient-reported outcomes were evaluated 1 week after treatment. RESULTS: A significant improvement (p < 0.001) for all clinical parameters was observed during the entire study period, with the exception of mean CAL gain for the laser 2 group at 12 months. The percentage of pockets ≤ 4 mm was significantly higher compared to baseline for all groups throughout the study, with no inter-group differences at any time point. Patient-reported analgesic consumption was higher for laser 1 group. CONCLUSIONS: The adjunctive use of Nd:YAG laser irradiation was similarly effective to FMS alone, during the entire study period. A slightly higher, though not statistically significant improvement was reported for PD at 6 and 12 months after a single post-FMS application of Nd:YAG laser for pocket epithelium removal and coagulation. CLINICAL RELEVANCE: Additional Nd:YAG laser application for sulcular epithelium removal and coagulation may provide minor long-term improvements compared to FMS or laser irradiation for pocket disinfection and detoxification. TRIAL REGISTRATION: ISRCTN26692900. Registration date: 09/06/2022.

ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically lll COVID-19 Patients.

BACKGROUND: Macrophage activation-like syndrome (MALS) and complex immune dysregulation (CID) often underlie acute respiratory distress (ARDS) in COVID-19. We aimed to investigate the effect of personalized immunotherapy on clinical improvement of critical COVID-19. METHODS: In this open-label prospective trial, 102 patients with ARDS by SARS-CoV-2 were screened for MALS (ferritin >4,420 ng/mL) and CID (ferritin ≤4,420 ng/mL and low human leukocyte antigen (HLA)-DR expression on CD14-monocytes). Patients with MALS or CID with increased aminotransferases received intravenous anakinra; those with CID and normal aminotransferases received tocilizumab. The primary outcome was ≥25% decrease in the Sequential Organ Failure Assessment (SOFA) score and/or 50% increase in the respiratory ratio by day 8; 28-day mortality, change of SOFA score by day 28, serum biomarkers, and cytokine production by mononuclear cells were secondary endpoints. RESULTS: The primary study endpoint was met in 58.3% of anakinra-treated patients and in 33.3% of tocilizumab-treated patients (p: 0.01). Most patients in both groups received dexamethasone as standard of care. No differences were found in secondary outcomes, mortality, and SOFA score changes. Ferritin decreased among anakinra-treated patients; interleukin-6, soluble urokinase plasminogen activator receptor, and HLA-DR expression increased among tocilizumab-treated patients. Survivors by day 28 who received anakinra were distributed to lower severity levels of the WHO clinical progression scale. Greater incidence of secondary infections was found with tocilizumab treatment. CONCLUSION: Immune assessment resulted in favorable anakinra responses among critically ill patients with COVID-19 and features of MALS.

Favorable Anakinra Responses in Severe Covid-19 Patients with Secondary Hemophagocytic Lymphohistiocytosis.

Dysregulation of inflammation is hypothesized to play a crucial role in the severe complications of COVID-19, with the IL-1/IL-6 pathway being central. Here, we report on the treatment of eight severe COVID-19 pneumonia patients-seven hospitalized in intensive care units (ICUs) in Greece and one non-ICU patient in the Netherlands-with the interleukin-1 receptor antagonist Anakinra. All patients scored positive for the hemophagocytosis score (HScore) and were diagnosed with secondary hemophagocytic lymphohistocytosis (sHLH) characterized by pancytopenia, hyper-coagulation, acute kidney injury, and hepatobiliary dysfunction. At the end of treatment, ICU patients had less need for vasopressors, significantly improved respiratory function, and lower HScore. Although three patients died, the mortality was lower than historical series of patients with sHLH in sepsis. These data suggest that administration of Anakinra may be beneficial for treating severe COVID-19 patients with sHLH as determined by the HScore, and they support the need for larger clinical studies to validate this concept.

Skin microcirculatory reactivity assessed using a thermal challenge is decreased in patients with circulatory shock and associated with outcome.

BACKGROUND: Shock states are characterized by impaired tissue perfusion and microcirculatory alterations, which are directly related to outcome. Skin perfusion can be noninvasively evaluated using skin laser Doppler (SLD), which, when coupled with a local thermal challenge, may provide a measure of microcirculatory reactivity. We hypothesized that this microvascular reactivity would be impaired in patients with circulatory shock and would be a marker of severity. METHODS: We first evaluated skin blood flow (SBF) using SLD on the forearm and on the palm in 18 healthy volunteers to select the site with maximal response. Measurements were taken at 37 °C (baseline) and repeated at 43 °C. The 43 °C/37 °C SBF ratio was calculated as a measure of microvascular reactivity. We then evaluated the SBF in 29 patients with circulatory shock admitted to a 35-bed department of intensive care and in a confirmatory cohort of 35 patients with circulatory shock. RESULTS: In the volunteers, baseline SBF was higher in the hand than in the forearm, but the SBF ratio was lower (11.2 [9.4-13.4] vs. 2.0 [1.7-2.6], p < 0.01) so we used the forearm for our patients. Baseline forearm SBF was similar in patients with shock and healthy volunteers, but the SBF ratio was markedly lower in the patients (2.6 [2.0-3.6] vs. 11.2 [9.4-13.4], p < 0.01). Shock survivors had a higher SBF ratio than non-survivors (3.2 [2.2-6.2] vs. 2.3 [1.7-2.8], p < 0.01). These results were confirmed in the second cohort of 35 patients. In multivariable analysis, the APACHE II score and the SBF ratio were independently associated with mortality. CONCLUSIONS: Microcirculatory reactivity is decreased in patients with circulatory shock and has prognostic value. This simple, noninvasive test could help in monitoring the peripheral microcirculation in acutely ill patients.

Primary thoracic muscle tuberculosis: two case reports.

BACKGROUND: The aim of this case report is to present our experience with two very rare cases of thoracic muscle tuberculosis. Muscle tuberculosis, as a primary disease, can only be detected in cases in which mycobacteria have been transplanted to a muscle through an infected needle. CASE PRESENTATIONS: Case 1 is a 38-year-old immigrant man and Case 2 is a 24-year-old immigrant man, both originating from Sub-Saharan African Countries; they presented in the past two years to our hospital with swellings at the base of the hemithorax and were diagnosed as having muscle tuberculosis. Administration of anti-tuberculosis chemotherapy caused: (a) diminution of inflammation, (b) diminution of the size of local fusiform injury, and (c) clinical improvement. CONCLUSIONS: Thoracic muscle tuberculosis should be considered to be one of the etiologies of muscular disease in European countries with a high incidence of immigrants originating from endemic geographical areas.

Colistin pharmacokinetics in intensive care unit patients on continuous venovenous haemodiafiltration: an observational study.

OBJECTIVES: Available data on colistin pharmacokinetics in patients undergoing continuous renal replacement therapy (CRRT) are limited. Our aim was to study colistin pharmacokinetics in critically ill patients treated with colistin methane sulphonate for Gram-negative sepsis and undergoing continuous venovenous haemodiafiltration for acute renal failure. PATIENTS AND METHODS: Three patients were studied. The colistin methane sulphonate dose administered was at the discretion of the attending physician and was in all cases lower than that recommended for individuals with intact renal function. Colistin methane sulphonate was administered intravenously over 30 min, and blood samples were collected from each patient pre- and post-filter for the HPLC determination of colistin levels in serum before infusion, at 10, 60, 120, 240, 360, 480 and 600 min from the end of infusion, and immediately before the next dose. Concurrently, spot samples of effluent from the haemofilter were also collected and analysed. Both colistin total extracorporeal clearance and clearance in the effluent were calculated. RESULTS: Extracorporeal clearance resulted in substantial removal of colistin (43%-59% of total colistin clearance). Total colistin clearance was found to be reduced (varying between 3.3 and 4.5 L/h), compared with patients with normal renal function. Colistin methane sulphonate dosage resulted in clearly suboptimal colistin steady-state concentrations. CONCLUSIONS: In spite of substantial extracorporeal clearance, total colistin clearance was reduced, compared with patients with normal renal function. Colistin adsorption by the haemofilter contributed to its extracorporeal clearance to a large extent. Studies on other patients receiving colistin methane sulphonate and undergoing CRRT are required before more appropriate dosage regimens can be recommended.

Increased blood troponin levels in ICU patients.

PURPOSE OF REVIEW: Cardiac troponins in serum have become the biomarkers of choice for the diagnosis of myocardial infarction. Yet, troponin can also be elevated by a multitude of causes in the absence of overt myocardial ischemia. Such nonspecific elevations are particularly common in the critically ill. This article aims to provide information on the significance of troponin elevations in unselected critically ill patients and in patients with sepsis or septic shock. RECENT FINDINGS: Recent studies reconsider the possible association of troponin elevations with myocardial infarction in unselected critically ill patients. There are also more data on the prognostic significance of troponin in this population. In patients with sepsis, recent studies suggest that troponin may be a reliable index of sepsis-induced myocardial dysfunction, although the implications of this finding in the management of sepsis remain unclear for the time being. Troponin also appears to be a predictor of short and possibly also long-term outcome in septic patients. The advent of newer assays with even higher sensitivity, may lead to further redefinition of the role of troponin in the ICU. SUMMARY: Troponin is frequently elevated in critically ill patients. More research is needed on the diagnostic and prognostic significance and possible clinical applications of troponin measurements in patients with sepsis and critical illness.

Rare roentgenologic manifestations of pulmonary edema.

PURPOSE OF REVIEW: Unilateral pulmonary edema (UPE) is an unusual manifestation of pulmonary edema that is frequently confused with other causes of unilateral alveolar and interstitial infiltrates. Until now limited data existed regarding the prevalence, cause, and outcome of patients presenting with cardiogenic UPE. The purpose of this review is to give insights into this rare entity. RECENT FINDINGS: In a recent retrospective study, the prevalence of UPE was 2.1% of all cases of cardiogenic pulmonary edema. UPE was right-sided in 89%. All patients with UPE had severe mitral regurgitation. In patients with UPE, blood pressure was significantly lower, whereas noninvasive or invasive ventilation and catecholamines were used more frequently compared with patients with bilateral pulmonary edema. In-hospital mortality was higher for patients with UPE (39 vs. 8% for bilateral pulmonary edema) and UPE was independently related to death (a 6.5-fold higher risk of death). Delayed treatment of UPE could be one of the explanations for this increased mortality. SUMMARY: UPE is not that rare as considered to be and is mostly related to severe organic or functional mitral regurgitation. Probably because of initial misdiagnosis and delayed appropriate treatment, UPE is related to increased mortality. History, absence of signs of infection, and elevated serum cardiac markers such as B-natriuretic peptide may help to differentiate UPE from other diagnoses. The key examination remains bedside transthoracic echocardiography, although transesophageal echocardiography can also provide additional information regarding the severity and mechanism of mitral regurgitation and documentation of the differential pressure between the right and left pulmonary veins.

The use of platelet-rich plasma combined with demineralized freeze-dried bone allograft in the treatment of periodontal endosseous defects: a report of two clinical cases.

BACKGROUND: On the basis of systematic reviews and randomized controlled trials, the authors provide reports of two cases in which platelet-rich plasma (PRP) combined with demineralized freeze-dried bone allograft (DFDBA) was used to treat periodontal endosseous defects. CASE DESCRIPTION: Clinicians treated two circumferential endosseous defects with a probing pocket depth of 5 and 8 millimeters, respectively (case 1), and a combined 1-2-3-wall endosseous defect with a probing pocket depth of 6 mm (case 2) by using the combination of PRP and DFDBA. At six months, complete periodontal pocket resolution occurred in all defects, and clinical attachment level and radiographic defect fill in all defects exhibited significant improvement compared with presurgical values. CLINICAL IMPLICATIONS: The combination of PRP and DFDBA may be clinically and radiographically efficacious in the treatment of periodontal endosseous defects.

Treatment of periodontal endosseous defects with platelet-rich plasma alone or in combination with demineralized freeze-dried bone allograft: a comparative clinical trial.

BACKGROUND: Platelet-rich plasma (PRP) alone or combined with other regenerative materials was previously studied in human periodontal endosseous defects. There are no sufficient data evaluating to what extent the addition of demineralized freeze-dried bone allograft (DFDBA) to PRP may enhance the effectiveness of PRP. The aim of this randomized, double-masked, controlled clinical trial was to compare the effectiveness of autologous PRP alone to PRP + DFDBA in periodontal endosseous defects. METHODS: Twenty-four proximal endosseous defects in 24 patients with severe chronic periodontitis were randomly treated with PRP alone or in combination with DFDBA. The final evaluation at 6 months was based on clinical and radiographic parameters. Subtraction radiography was used. The primary outcome variable was clinical attachment level (CAL). RESULTS: The two treatment groups were initially comparable (mean CAL: 8.67 +/- 2.19 mm for PRP + DFDBA and 8.25 +/- 1.96 mm for PRP). Both treatments achieved statistically significant and similar CAL gain (3.08 +/- 1.17 mm for PRP + DFDBA and 3.08 +/- 0.95 mm for PRP), probing depth, defect depth, and area surface reduction. The percentage of defect fill did not significantly differ between the two treatments. There was a non-significant trend to greater defect fill (45.42% versus 41.29%), defect depth (54.05% versus 49.52%), and area surface (58.43% versus 52.16%) reduction with the graft. In both groups, 66.66% of the defects gained > or =3 mm of CAL. CONCLUSION: Within its limits, this study demonstrates that both PRP and PRP combined with DFDBA resulted in significant clinical and radiographic improvement in human periodontal endosseous defects at 6 months, and the addition of DFDBA to PRP did not significantly enhance the treatment outcome.

Near-drowning: clinical course of lung injury in adults.

BACKGROUND AND OBJECTIVES: Although anoxic encephalopathy is the most dreaded consequence of submersion accidents, respiratory involvement is also very common in these patients. Nevertheless, few data are available about the clinical course and resolution of lung injury in adult victims of near-drowning. Our goal was to study the clinical manifestations of near-drowning and the course of respiratory involvement in a retrospective cohort of adult, mostly elderly patients. PATIENTS: Our study included adult patients who were hospitalized after near-drowning in seawater over an 8-year period. Forty-three patients (26 female, 17 male), with an age range of 18-88 years old, were studied. Most (79%) of the patients were elderly (>60 years). RESULTS: In the Emergency Department two patients were comatose and required intubation. Another patient was intubated within the first 24 h because of ARDS. At presentation, all patients but two had a PaO(2)/FiO(2) < 300, while ARDS was present in 17 and acute lung injury in 15 cases. The nine remaining hypoxemic patients had either focal infiltrates or a negative chest X-ray. Superimposed pneumonia was observed in four patients and resulted in a protracted hospital stay. Improvement of lung injury was rapid in most cases: by day 4 resolution of hypoxemia was observed in 33/43 (76.7%) of the cases and resolution of radiographic findings in 66.6%. Duration of hospitalization varied from 2 to 14 days (mean = 5.2 +/- 0.5 days). One patient with coma died due to ventilator-associated pneumonia (mortality = 2.3%). CONCLUSION: Respiratory manifestations of near-drowning in adult immersion victims are often severe. Nevertheless, in noncomatose patients at least, intubation can often be avoided and quick improvement is the rule while a good outcome is usually expected even in elderly patients.

Combined nutritional support in patients with chronic obstructive pulmonary disease (COPD), under mechanical ventilation (MV).

BACKGROUND/AIMS: The importance of nutrition is clearly established in the management of the critically ill patient: malnutrition contributes to immune incompetence, poor wound healing, increased postoperative complication and prolonged hospital stay. The interaction between nutritional status, nutritional supply and respiratory function is important in the management of the Chronic Obstructive pulmonary Disease (COPD) patients under mechanical ventilation (MV). In the present study was analyzed the benefits of combined nutritional support in patients with COPD under MV. METHODOLOGY: One hundred ninety two (192) patients with COPD were admitted to our Intensive Care Unit (ICU), due to severe respiratory failure of whom 163 (84.9%) patients were under MV. In 18 (11.04%) patients after the 10th day under MV and due to severe malnutrition (serum albumin < 2.5 gm/dl, total lymphocyte count (TLC) < 900/mm3), added in the enteral nutrition (EN) of 1800 Kcals and parenteral nutrition (PN) of 2000 Kcals, at high concentration in lipids from central venous catheter. RESULTS: Seven (38.89%) patients on the 4th day, after combined nutrition, had a positive balance of nitrogen and normal level of the nutritional indices, 4 (22.22%) were on normal level on the 5th day, 3 (16.67%) on the 6th day, 1 (5.56%) on the 7th day after combined nutrition. We had no complications from the combination of EN and PN. Conclusively, of these 18 patients that were given both EN and PN, 15 (83.33%) were weaned from MV and continued the combined nutritional support for 3 days, while 3 (16.67%) died during the combination of EN and PN, without having achieved a normal level of the indices of nutrition and without a positive balance of nitrogen. CONCLUSIONS: In this study was found that: 1. patients with COPD under MV rapidly developed malnutrition, 2. the combination EN and PN without complications contribute to the weaning from MV, 3. positive nitrogen balance and normal increases of nutrition are achieved after the 4th day of combined nutrition and 4. Early addition of EN and PN in patients with COPD under MV, probably accelerates the weaning from MV, reduces hospitalization, changes the outcome and reduces the cost of hospitalization of patients with COPD under MV in ICU.

Colistin serum concentrations after intravenous administration in critically ill patients with serious multidrug-resistant, gram-negative bacilli infections: a prospective, open-label, uncontrolled study.

BACKGROUND: The emergence of multidrug-resistant nosocomial pathogens, such as Pseudomonas aeruginosa and Acinetobacter baumannii, has led to the revival of the systemic use of antimicrobial agent colistin in critically ill patients, but only limited data are available to define its pharmacokinetic profile in these patients. OBJECTIVE: The aim of this study was to assess steady-state serum concentrations of colistin after i.v. administration of colistin methanesulfonate (CMS) in critically ill patients with stable kidney function. METHODS: This prospective, open-label, uncontrolled study was conducted at 2 intensive care units in the Athens Trauma Hospital, KAT, Athens, Greece. Adult patients were nonconsecutively enrolled if they were critically ill and had stable kidney function (<0.5 mg/dL change in serum creatinine prior to and until the day of sample collection) and had been receiving CMS as part of a treatment regimen for sepsis irrespective of site of infection with multidrug-resistant, gram-negative bacilli. After i.v. administration of 225-mg CMS (with the exception of 1 patient who received 150 mg) every 8 or 12 hours for at least 2 days, blood samples were collected just before and at 10 minutes and 1, 2, 4, 6, and 8 hours after i.v. infusion (duration, 30 minutes) of the colistin dose on the sampling day. RESULTS: Fourteen nonconsecutive patients were enrolled in the study (13 male, 1 female; mean [SD] age, 62.0 [19.2] years; mean [SD] estimated weight, 72.5 [8.5] kg; mean [SD] Acute Physiology And Chronic Health Evaluation II score on admission, 17.1 [6.0]). At steady state, mean (SD) colistin maximum and minimum concentrations were 2.93 (1.24) and 1.03 (0.44) mg/L, respectively, while mean (SD) apparent total body clearance, apparent volume of distribution, and t(1/2) were 13.6 (5.8) L/h, 139.9 (60.3) L, and 7.4 (1.7) hours, respectively. Colistin-related nephrotoxicity was not observed in the study patients. CONCLUSION: CMS dosage regimens administered to these critically ill adult patients were associated with suboptimal Cmax/MIC ratios for many strains of gram-negative bacilli currently reported as sensitive (MIC, < or = 2 microg/mL).