amphotericin-b and Critical-Illness

Invasive candidiasis is the most common fungal infection affecting critically ill adults. International guidelines provide differing recommendations for first-line antifungal therapy, with echinocandins considered first-line in the majority. Amphotericin B has broad activity and low minimum inhibitory concentration resistance patterns across most Candida species and guidance away from its use should be supported by the available evidence. Areas Covered: A systematic literature review was conducted from August to September 2017 to determine whether treatment with echinocandins or other available drugs, namely voriconazole, confers a therapeutic or survival benefit over amphotericin B in critically ill adults with invasive candidiasis. Inclusion criteria were: (1) studies describing critically ill adults with invasive candidiasis, (2) studies describing therapeutic benefit or survival as an outcome, and (3) studies comparing amphotericin B, deoxycholate or lipid preparations, with any newer antifungal agent. Eight studies were included in the final review, incorporating 2352 unique patients. No difference in treatment efficacy or mortality outcomes in critically ill patients with invasive candidiasis receiving an amphotericin B formulation compared with those receiving an echinocandin or voriconazole was shown. Expert Commentary: We conclude that in the existing literature, there is no evidence that choice between echinocandins, voriconazole, or amphotericin B formulations as first-line therapy for critically ill adults with invasive candidiasis is associated with a therapeutic or survival benefit. Clinicians must therefore consider other factors in the selection of first-line therapy.

Topics: Adult; Amphotericin B; Antifungal Agents; Candida; Candidemia; Candidiasis, Invasive; Critical Illness; Humans; Microbial Sensitivity Tests; Practice Guidelines as Topic

Invasive fungal infections are important causes of morbidity and mortality among critically ill patients. Early institution of antifungal therapy is pivotal for mortality reduction. Starting a targeted antifungal therapy after culture positivity and fungi identification requires a long time. Therefore, alternative strategies (globally defined as 'untargeted antifungal treatments') for antifungal therapy institution in patients without proven microbiological evidence of fungal infections have been discussed by international guidelines. This review was originally published in 2006 and updated in 2016. This updated review provides additional evidence for the clinician dealing with suspicion of fungal infection in critically ill, non-neutropenic patients, taking into account recent findings in this field.. To assess the effects of untargeted treatment with any antifungal drug (either systemic or nonabsorbable) compared to placebo or no antifungal or any other antifungal drug (either systemic or nonabsorbable) in non-neutropenic, critically ill adults and children. We assessed effectiveness in terms of total (all-cause) mortality and incidence of proven invasive fungal infections as primary outcomes.. We searched the following databases to February 2015: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OVID), and EMBASE (OVID). We also searched reference lists of identified studies and major reviews, abstracts of conference proceedings, scientific meetings and clinical trials registries. We contacted experts in the field, study authors and pharmaceutical companies as part of the search strategy.. We included randomized controlled trials (RCTs) (irrespective of language or publication status) comparing the use of untargeted treatment with any antifungal drug (either systemic or nonabsorbable) to placebo, no antifungal, or another antifungal agent in non-neutropenic critically ill participants.. Three authors independently applied selection criteria, extracted data and assessed the risk of bias. We resolved any discrepancies by discussion. We synthesized data using the random-effects model and expressed the results as risk ratios (RR) with 95% confidence intervals. We assessed overall evidence quality using the GRADE approach.. We included 22 studies (total of 2761 participants). Of those 22 studies, 12 were included in the original published review and 10 were newly identified. Eleven trials compared the use of fluconazole to placebo or no antifungal treatment. Three trials compared ketoconazole versus placebo. One trial compared anidulafungin with placebo. One trial compared caspofungin to placebo. Two trials compared micafungin to placebo. One trial compared amphotericin B to placebo. Two trials compared nystatin to placebo and one trial compared the effect of clotrimazole, ketoconazole, nystatin and no treatment. We found two new ongoing studies and four new studies awaiting classification. The RCTs included participants of both genders with wide age range, severity of critical illness and clinical characteristics. Funding sources from pharmaceutical companies were reported in 11 trials and one trial reported funding from a government agency. Most of the studies had an overall unclear risk of bias for key domains of this review (random sequence generation, allocation concealment, incomplete outcome data). Two studies had a high risk of bias for key domains. Regarding the other domains (blinding of participants and personnel, outcome assessment, selective reporting, other bias), most of the studies had a low or unclear risk but four studies had a high risk of bias.There was moderate grade evidence that untargeted antifungal treatment did not significantly reduce or increase total (all-cause) mortality (RR 0.93, 95% CI 0.79 to 1.09, P value = 0.36; participants = 2374; studies = 19). With regard to the outcome of proven invasive fungal infection, there was low grade evidence that untargeted antifungal treatment significantly reduced the risk (RR 0.57, 95% CI 0.39 to 0.83, P value = 0.0001; participants = 2024; studies = 17). The risk of fungal colonization was significantly reduced (RR 0.71, 95% CI 0.52 to 0.97, P value = 0.03; participants = 1030; studies = 12) but the quality of evidence was low. There was no difference in the risk of developing superficial fungal infection (RR 0.69, 95% CI 0.37 to 1.29, P value = 0.24; participants = 662; studies = 5; low grade of evidence) or in adverse events requiring cessation of treatment between the untargeted treatment group and the other group (RR 0.89, 95% CI 0.62 to 1.27, P value = 0.51; participants = 1691; studies = 11; low quality of evidence). The quality of evidence for the outcome of total (all-cause) mortality was moderate. There is moderate quality evidence that the use of untargeted antifungal treatment is not associated with a significant reduction in total (all-cause) mortality among critically ill, non-neutropenic adults and children compared to no antifungal treatment or placebo. The untargeted antifungal treatment may be associated with a reduction of invasive fungal infections but the quality of evidence is low, and both the heterogeneity and risk of publication bias is high.Further high-quality RCTs are needed to improve the strength of the evidence, especially for more recent and less studied drugs (e.g. echinocandins). Future trials should adopt standardized definitions for microbiological outcomes (e.g. invasive fungal infection, colonization) to reduce heterogeneity. Emergence of resistance to antifungal drugs should be considered as outcome in studies investigating the effects of untargeted antifungal treatment to balance risks and benefit.

Topics: Adult; Amphotericin B; Antifungal Agents; Critical Illness; Fluconazole; Humans; Immunocompromised Host; Mycoses; Randomized Controlled Trials as Topic

Candida infections represent challenging causes of severe sepsis and/or of septic shock in the critically ill patients. Knowledge of current pharmacological concepts may promote a more wise use of echinocandins in the management of Candida infections in this setting. Echinocandins have some advantages over azoles, both pharmacodynamically (rapid fungicidal activity, anti-biofilm activity, unmodified activity against Candida isolates with decreased susceptibility to azoles and anti-cytokine/anti-chemokine activity) and pharmacokinetically (low interindividual variability, low potential for drug-drug interactions), that may influence the timing and the choice of therapy of Candida diseases in the critically ill patients. However, concerns exist in regards to the feasibility of fixed dosing regimens of echinocandins in all of the different patient populations and in regards to the effectiveness of echinocandin monotherapy in some clinical settings. In presence of deep-seated infections, voriconazole or liposomal amphotericin B may be valuable alternatives or add-on therapy.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Critical Illness; Drug Administration Schedule; Drug Dosage Calculations; Drug Therapy, Combination; Echinocandins; Humans; Practice Guidelines as Topic; Pyrimidines; Sepsis; Triazoles; Voriconazole

Currently there are three main drug groups for the prevention and treatment of fungal infections: polyenes (amphotericin B deoxycholate or its lipid formulations), azoles (fluconazole, itraconazole or posaconazole) and echinocandins (caspofungin, micafungin and anidulafungin). However, a major characteristic to be evaluated when choosing an antifungal agent -apart from antifungal spectrum, pharmacokinetics and adverse effects- is the absence of significant drug interactions. Amphotericin B lacks interactions but may cause renal dysfunction, leading to the accumulation of renally metabolized drugs. Nephrotoxicity is significantly lower with lipid formulations, especially with liposomal amphotericin B. Azoles modify the metabolism of a wide range of drugs by inhibiting their biotransformation or altering their distribution and elimination. These drugs are metabolized in the liver through the P450 cytochrome complex, inhibiting several isoenzymes, especially CYP3A4, the main drug-metabolizing enzyme. Moreover, itraconazole and posaconazole are substrates and inhibitors of the transporter protein, P-glycoprotein. Fluconazole is the azole with the fewest drug-drug interactions. The echinocandins have increased the therapeutic arsenal and a particular feature of these drugs is their safety, due to the absence of severe adverse effects and the scarce number of interactions. The echinocandin with the highest number of interactions is caspofungin. Micafungin is an echinocandin lacking in relevant interactions and consequently its dosage requires no adjustment in any of its indications. This drug can be used both in adults and in the pediatric population, including neonates.

Topics: Adult; Amphotericin B; Antifungal Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; Child; Critical Illness; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Drug Therapy, Combination; Echinocandins; Humans; Infant, Newborn; Lipopeptides; Micafungin; Microsomes, Liver; Mycoses; Triazoles

Acute kidney injury is common in critically ill patients, with an incidence of 20% to 30%. It has been associated with increased mortality, hospital length of stay, and total cost. A number of strategies may be beneficial in identifying at-risk patients. In addition, using preventive measures and avoiding nephrotoxic medications are paramount in reducing the overall incidence. Although multifactorial, drug-induced acute kidney injury may account for up to 25% of all cases of acute kidney injury in this population. This review focuses on the mechanisms of drug-induced acute kidney injury in critically ill adults and offers preventive strategies when appropriate.

Topics: Acute Kidney Injury; Adult; Aminoglycosides; Amphotericin B; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Antifungal Agents; Calcineurin Inhibitors; Contrast Media; Critical Care; Critical Illness; Cyclooxygenase Inhibitors; Decision Support Systems, Clinical; Drug-Related Side Effects and Adverse Reactions; Humans; Medical Order Entry Systems

The most frequent invasive fungal infections in critically ill patients are invasive candidiasis, among which is candidemia. In the last few years, these infections have become more common in intensive care units (ICU), including those produced by species other than Candida albicans. This phenomenon may lead to the development of species resistant to antifungal agents. To start the most appropriate treatment, early diagnosis of the infection is essential, which would reduce empirical antibiotic treatment and increase the proportion of advanced or directed antibiotic therapy. Given the poor reliability of the available diagnostic techniques, new strategies are currently being employed in the ICU, such as the use of scores to evaluate the presence of fungal infections. The therapeutic arsenal against these infections has been increased and the introduction of anidulafungin represents the addition of a highly appropriate drug for the treatment of invasive candidiasis in immunocompetent critically ill patients.

Topics: Amphotericin B; Anidulafungin; Antifungal Agents; Candidiasis; Clinical Trials as Topic; Critical Illness; Cross Infection; Drug Therapy, Combination; Echinocandins; Fluconazole; Fungemia; Humans; Immunocompetence; Intensive Care Units; Itraconazole; Practice Guidelines as Topic

Bloodstream infections caused by Candida spp. are increasingly recognised in critically ill adult and paediatric individuals, with significant associated morbidity and mortality. Candida albicans is the single most common fungal species to cause nosocomial infections. However, non-C. albicans spp., including Candida glabrata and Candida krusei, which are less susceptible to fluconazole, have become more common. Until the 1980s, the therapeutic possibilities for invasive candidosis were limited to amphotericin B, but with the advent of new antifungal agents, such as azoles and echinocandins, less toxic therapeutic options have become available and there are now possibilities for prevention and optimised therapy for documented Candida infections. In this review, the currently available options for the treatment of candidaemia and invasive candidosis are discussed with regard to the role of liposomal amphotericin B in comparison with the echinocandins and azoles.

Topics: Amphotericin B; Antifungal Agents; Azoles; Candida; Candidiasis; Caspofungin; Critical Illness; Cross Infection; Drug Therapy, Combination; Echinocandins; Fungemia; Humans; Lipopeptides

Invasive fungal infections, important causes of morbidity and mortality in critically ill patients, may be preventable with the prophylactic administration of antifungal agents.. This study aims to systematically identify and summarize the effects of antifungal prophylaxis in non-neutropenic critically ill adult patients on all-cause mortality and the incidence of invasive fungal infections.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library, Issue 3, 2005), MEDLINE (1966 to 2 September 2005), and EMBASE (1980 to week 36, 2005). We also handsearched reference lists, abstracts of conference proceedings and scientific meetings (1998 to 2004), and contacted authors of included studies and pharmaceutical manufacturers.. We included randomized controlled trials in all languages comparing the prophylactic use of any antifungal agent or regimen with placebo, no antifungal, or another antifungal agent or regimen in non-neutropenic critically ill adult patients.. Two authors independently applied selection criteria, performed quality assessment, and extracted data using an intention-to-treat approach. We resolved differences by discussion. We synthesized data using the random effects model and expressed results as relative risk with 95% confidence intervals.. We included 12 unique trials (eight comparing fluconazole and four ketoconazole with no antifungal or a nonabsorbable agent) involving 1606 randomized patients. For both outcomes of total mortality and invasive fungal infections, almost all trials of fluconazole and ketoconazole separately showed a non-significant risk reduction with prophylaxis. When combined, fluconazole/ketoconazole reduced total mortality by about 25% (relative risk 0.76, 95% confidence interval 0.59 to 0.97) and invasive fungal infections by about 50% (relative risk 0.46, 95% confidence interval 0.31 to 0.68). We identified no significant increase in the incidence of infection or colonization with the azole-resistant fungal pathogens Candida glabrata or C. krusei, although the confidence intervals of the summary effect measures were wide. Adverse effects were not more common amongst patients receiving prophylaxis. Results across all trials were homogeneous despite considerable heterogeneity in clinical and methodological characteristics.. Prophylaxis with fluconazole or ketoconazole in critically ill patients reduces invasive fungal infections by one half and total mortality by one quarter. Although no significant increase in azole-resistant Candida species associated with prophylaxis was demonstrated, trials were not powered to exclude such an effect. In patients at increased risk of invasive fungal infections, antifungal prophylaxis with fluconazole should be considered.

Topics: Adult; Amphotericin B; Antifungal Agents; Critical Illness; Fluconazole; Humans; Immunocompromised Host; Mycoses; Randomized Controlled Trials as Topic

The high morbidity, mortality, and healthcare costs associated with the invasive fungal infections, especially in the critical care setting, is of importance since the prophylactic, empiric, and pre-emptive therapy interventions, based on early identification of risk factors, is of common occurrence. In the last years alone there have been important developments in antifungal pharmacotherapy. Evidence-based studies using new antifungal agents are now emerging as important players in the pharmacotherapy of invasive fungal infections in seriously ill and difficult patients. However, data on critically ill patients are more limited and usually recovered from general studies. This study shows the benefits obtained by the new antifungal agents on different clinical situations in critical care units. The increasing number of non-C. albicans species and the high mortality rates in these settings suggest that the application of early de-escalation therapy in critically ill patients with fungal infection should be mandatory. The possibility of using antifungal combination therapy in these types of patients should be considered.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Critical Illness; Cross Infection; Deoxycholic Acid; Drug Combinations; Fluconazole; Humans; Intensive Care Units; Mycoses; Pyrimidines; Randomized Controlled Trials as Topic; Triazoles; Voriconazole

Invasive candidiasis is a feared infection with mortality similar to that of septic shock (40-60%). Improved knowledge of its pathophysiology and the availability of new compounds for antifungal therapy and prophylaxis have contributed to improving the prognosis of severe candidal infections among immunosuppressed patients at the possible cost of the emergence of non-albicans strains of candida with lower susceptibility to azoles. This review focuses on the management of invasive deep-seated candidiasis in critically ill, non-immunocompromised patients. We discuss antifungal use, indications, potential benefit, and main secondary effects. Prevention strategies include pre-emptive antifungal therapy and azole-based prophylaxis. For patients at lower initial risk, pre-emptive therapy should be based on a management strategy that takes into account the presence of definite risk factors and the dynamics of candida colonisation. Among critically ill patients, azole prophylaxis is effective and is not associated with acquisition of resistance; it must be restricted to highly selected groups of patients at high risk only.

Topics: Amphotericin B; Antifungal Agents; Azoles; Candidiasis; Clinical Trials as Topic; Critical Illness; Humans; Immunocompetence; Nystatin; Practice Guidelines as Topic

Renal and electrolyte problems are common in patients in the ICU. Several advances that occurred in the recent past have been incorporated in the diagnosis and management of these disorders and were reviewed in this article. Unfortunately, many important questions remain unanswered, especially in the area of ARF, where new therapies are anxiously awaited to make the transition from bench to bedside. Better studies are sorely needed to define the best approach to dialysis in patients who have ARF.

Topics: Acid-Base Imbalance; Acute Kidney Injury; Alkalosis; Amphotericin B; Antifungal Agents; Cardiotonic Agents; Critical Care; Critical Illness; Dopamine; Humans; Kidney Diseases; Renal Dialysis; Sodium Bicarbonate

Selective decontamination of the digestive tract (SDD) is a strategy designed to prevent or minimize the impact of infections by potentially pathogenic micro-organisms in critically ill patients requiring long-term mechanical ventilation. SDD is a four-component protocol to control the three types of infections occurring in intensive care patients: (a) a parenteral antibiotic, cefotaxime, for a few days to prevent primary endogenous infections that generally occur 'early'; (b) the topical antimicrobial drugs colistine (polymyxin E), tobramycin and amphotericin B (together: PTA) used throughout the stay in the intensive care unit (ICU) to prevent secondary endogenous infections developing in general 'late'; (c) a high standard of hygiene to prevent exogenous infections that may occur throughout the ICU stay; (d) surveillance samples of throat and rectum to distinguish between the three types of infection, to monitor compliance and efficacy of treatment and to detect emergence of resistance at an early stage. The most recent and rigorous meta-analysis examined 33 randomized SDD trials involving 5727 patients. It shows significant reductions, in overall mortality by 20% and in the incidence of lower airway infections by 65%. It failed to detect any report on the emergence of resistance and associated superinfections and/or out-breaks in the 33 studies covering a period of more than 10 years. Using the criterion of cost-per-survivor, four recent randomised trials showed that it is cheaper to produce a survivor using SDD than with the traditional approach.

Topics: Amphotericin B; Bacterial Infections; Cefotaxime; Clinical Protocols; Colistin; Critical Care; Critical Illness; Cross Infection; Decontamination; Digestive System; Drug Therapy, Combination; Female; Humans; Intensive Care Units; Male; Survival Rate; Tobramycin

We report a fatal case of invasive pulmonary aspergillosis in a severely ill neonate and review 43 additional cases of invasive aspergillosis reported from 1955 through 1996 that occurred during the first 3 months of life. Eleven of the 44 patients had primary cutaneous aspergillosis, 10 had invasive pulmonary aspergillosis, and 14 had disseminated disease. Most infections were nosocomial in origin. Prematurity (43%); proven chronic granulomatous disease (14%); and a complex of diarrhea, dehydration, malnutrition, and invasive bacterial infections (23%) accounted for the majority of underlying conditions. At least 41% of the patients had received corticosteroid therapy before diagnosis, but only one patient had been neutropenic. Among patients who received medical and/or surgical treatment, outcome was relatively favorable, with an overall survival rate of 73%. Invasive aspergillosis may occur in neonates and young infants and warrants consideration under certain circumstances. Current therapeutic approaches consist of high-dose amphotericin B and appropriate surgical interventions.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Central Nervous System Diseases; Critical Illness; Cross Infection; Dermatomycoses; Fatal Outcome; Gastrointestinal Diseases; Humans; Infant; Infant, Newborn; Lung Diseases; Male

Four patients with underlying diseases including multiple trauma, aortic graft infection, and complex fistulae developed acute acalculous cholecystitis with bile cultures positive only for Candida albicans. The primary site of the candida infection included urinary tract, gastrointestinal tract, and an aortic graft in one patient each and was undetermined in the trauma victim. All had received broad-spectrum antibiotics; three of the four were in the intensive care unit (ICU) with organ failure. Ultrasonography showed a thickened gallbladder wall in three patients and sludge in one. Hepato-iminodiacetic acid scans were nonvisualizing in these three patients. Operative findings included gangrenous cholecystitis in two patients and edematous cholecystitis in one. The fourth patient was treated with percutaneous cholecystostomy and interval cholecystectomy. The interval from the onset of symptoms to recognition of the need for operation was an average of 7 days. Two of the four patients died of ongoing sepsis. Candida cholecystitis is a life-threatening complication of critical surgical illness. Risk factors are similar to those for candida infection elsewhere and include antibacterial therapy, complex fistulae, disseminated malignancy, immunosuppression, and prolonged ICU stay. A high index of suspicion for this fungal pathogen and aggressive surgical therapy offer the only chance for a favorable outcome.

Topics: Acute Disease; Adult; Aged; Amphotericin B; Candidiasis; Cholecystectomy; Cholecystitis; Cholecystostomy; Cholelithiasis; Critical Illness; Disease; Female; Humans; Male; Middle Aged; Postoperative Complications; Risk Factors; Surgical Procedures, Operative

Intra-abdominal candidiasis (IAC) has a high mortality rate. However, the correct management of a critically ill patient with suspected IAC remains unclear. The aim of this study was to evaluate the safety of pulsed high-dose liposomal amphotericin B (L-AmB) in patients with suspected IAC managed with a beta-D-glucan (BDG)-guided strategy.. This phase 2 prospective study enrolled adult patients with intra-abdominal sepsis following surgery. Patients received a single dose of L-AmB 5 mg/kg on day 1. On day 3, L-AmB was discontinued in patients with a negative basal BDG result, and continued (3 mg/kg/daily) in patients with a positive basal BDG result or microbiologically confirmed IAC. The primary endpoint was the occurrence of adverse events, defined using the Common Toxicity Criteria classification.. In total, 40 patients were enrolled from January 2019 to August 2022. Fifteen (37.5%) patients were male, and the median age was 65 [interquartile range (IQR) 49-76] years. Thirty-one (77.5%) patients underwent urgent surgery, and the principal indication was secondary/tertiary peritonitis (n=22, 55%); half of the patients had undergone a previous surgical operation within the preceding 30 days. Five (12.5%) patients met the criteria for septic shock at enrolment. The median APACHE II score on admission to the intensive care unit was 12 (IQR 10-15). IAC was excluded in 33 (85%) patients, but IAC was probable and proven in five (12.5%) and two (5%) patients, respectively. The single dose of L-AmB 5 mg/kg was well tolerated in all patients, and no early or late severe adverse events related to the drug were reported. L-AmB was discontinued in 65% of patients following a negative basal BDG result. The all-cause 30-day mortality rate was 15%, and no deaths were related to L-AmB administration or uncontrolled IAC. The mortality rates for patients with and without proven IAC were 0% and 15.8%, respectively (P=0.99).. The rate of proven IAC among critically ill high-risk patients was low (5%). A single dose of L-AmB 5 mg/kg, with prompt withdrawal in the case of a basal negative BDG result, seems to be a safe and effective approach in this population.

Topics: Adult; Aged; Antifungal Agents; Candidiasis; Critical Illness; Female; Humans; Male; Middle Aged; Peritonitis; Prospective Studies

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Critical Illness; Humans; Middle Aged; Pilot Projects; Treatment Outcome

The penetration of the amphotericin B (AMB) lipid formulations (liposomal AMB, AMB colloidal dispersion, and AMB lipid complex formulations) into pleural effusions in seven critically ill patients was assessed. AMB was detected in all pleural effusion samples at concentrations ranging from 0.02 to 0.43 microg/ml. The penetration ratio was 3 to 44%.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Critical Illness; Drug Combinations; Female; Humans; Male; Middle Aged; Phosphatidylcholines; Phosphatidylglycerols; Pleural Effusion

The prevalence of Helicobacter pylori is increased in healthcare workers and in intensive care nurses. Exposure to H. pylori from gastric secretions and faeces are probably the main sources of transmission to healthcare workers. Routine use of selective decontamination of digestive tract (SDD) in an intensive care unit suppresses H. pylori in critically ill patients. It was questioned whether this suppression and the subsequent decreased exposure to H. pylori for intensive care nurses would lead to a lower prevalence of H. pylori infection. Helicobacter pylori infection prevalence in intensive care nurses from a unit routinely using SDD (group I) was compared to that of nurses from a unit not using SDD (group II). Heathcare workers from other departments of the hospital where no SDD was used (group III) served as a control group. Persons using proton pump inhibitors were excluded. Helicobacter pylori was detected by Laser Assisted Ratio Analyser(13)C-urea breath test (UBT) and serology. This could not be performed in three out of 64 in group I, five out of 55 in group II and five out of 55 in group III (total UBTs = 169). The prevalence of H. pylori infection was 11% (7/61) in group I and 25.5% (14/50) in group II (P= 0.027). In group III, the prevalence of H. pylori infection was 16% (8/45), which was not significantly different from both group I and II. Sero-prevalence in group I was 18.6%, 27% in group II (ns) and 24% in group III. Mean age in the three groups was 35.9, 37.8 and 36.6 years, respectively (ns). In conclusion, the prevalence of H. pylori infection among intensive care nurses is lower in nurses from a unit using SDD compared to a non SDD-using unit. Acquisition of H. pylori by transmission from critically ill patients appears to be diminished through SDD use.

Topics: Adult; Amphotericin B; Breath Tests; Colistin; Critical Care; Critical Illness; Cross Infection; Cross-Sectional Studies; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Infection Control; Infectious Disease Transmission, Patient-to-Professional; Nursing Staff, Hospital; Prevalence; Stomach Diseases; Tobramycin

To determine the incidence and prognosis of candidemia in non-neutropenic critically ill patients, to define mortality-related factors, and to evaluate the results of systemic antifungal therapy.. A prospective multicenter survey in which medical and/or surgical intensive care units (ICUs) in 28 hospitals in Spain participated.. All critically ill patients with positive blood cultures for Candida species admitted to the participating ICUs over a 15-month period were included.. Candidemia was defined as the presence of at least one positive blood culture containing Candida species. The follow-up period was defined as the time elapsed from the first positive blood culture for Candida species to discharge or death during hospitalization. Antifungal therapy was considered to be "early" when it was administered within 48 h of the date when the first positive blood culture was obtained and "late" when it was administered more than 48 h after the first positive blood culture.. Candidemia was diagnosed in 46 patients (mean age 59 years), with an incidence of 1 critically ill patient per 500 ICU admissions. The species most frequently isolated were Candida albicans (60%) and C. parapsilosis (17%). Fluconazole alone was given to 27 patients, amphotericin B alone to 10, and sequential therapy to 6. Three patients did not receive antifungal therapy. The overall mortality was 56% and the attributable mortality 21.7%. In the univariate analysis, mortality was significantly associated with a higher Acute Physiology and Chronic Health Evaluation (APACHE) II score at the onset of candidemia (p = 0.04) and with the time elapsed between the episode of candidemia and the start of antifungal therapy 48 h or more later (p < 0.02). Patients with an APACHE II score lower than 21 at the onset of candidemia had a higher probability of survival than patients who were more seriously ill (p = 0.04). Patients with "early" antifungal therapy (< or = 48 h between the onset of candidemia and the start of antifungal therapy) had a higher probability of survival compared with patients with late therapy (p = 0.06). No significant differences were noted between the two groups on different antifungal therapy.. The incidence of candidemia in ICU patients was very low. An APACHE II score > 20 at the time of candidemia was associated with a higher mortality. Further studies with a large number of patients are needed to assess the effect of early antifungal therapy on the decrease in mortality associated with candidemia and to determine the appropriate dosage of fluconazole and duration of treatment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; APACHE; Candidiasis; Critical Illness; Cross Infection; Data Interpretation, Statistical; Female; Fluconazole; Fungemia; Humans; Incidence; Intensive Care Units; Male; Middle Aged; Prognosis; Prospective Studies; Spain

The liposomal formulation of amphotericin B (AmBisome) greatly reduces the acute and chronic side effects of the parent drug. The present study describes the pharmacokinetic characteristics of AmBisome applied to 10 patients at a dose of 2.8 to 3.0 mg/kg of body weight and compares them to the pharmacokinetics observed in 6 patients treated with amphotericin B deoxycholate at the standard dose of 1.0 mg/kg. Interpatient variabilities of amphotericin B peak concentrations (Cmax) and areas under concentration-time curves (AUC) were 8- to 10-fold greater for patients treated with AmBisome than for patients treated with amphotericin B deoxycholate. At the threefold greater dose of AmBisome, median Cmaxs were 8.4-fold higher (14.4 versus 1.7 microg/ml) and median AUCs exceeded those observed with amphotericin B deoxycholate by 9-fold. This was in part explained by a 5.7-fold lower volume of distribution (0.42 liters/kg) in AmBisome-treated patients. The elimination of amphotericin B from serum was biphasic for both formulations. However, the apparent half-life of elimination was twofold shorter for AmBisome (P = 0.03). Neither hemodialysis nor hemofiltration had a significant impact on AmBisome pharmacokinetics as analyzed in one patient. In conclusion, the liposomal formulation of amphotericin B significantly (P = 0.001) reduces the volume of drug distribution, thereby allowing for greater drug concentrations in serum. The low toxicity of AmBisome therefore cannot readily be explained by its serum pharmacokinetics.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Antiprotozoal Agents; Critical Illness; Deoxycholic Acid; Dialysis; Dose-Response Relationship, Drug; Drug Carriers; Drug Combinations; Drug Interactions; Fat Emulsions, Intravenous; Female; Hemofiltration; Humans; Liposomes; Male; Middle Aged

To evaluate the differences in efficacy and in clinical and biochemical tolerance to amphotericin B administered in a lipid emulsion compared with amphotericin B administered in 5% dextrose in water in the treatment of Candida albicans infection in intensive care unit (ICU) patients.. Prospective, controlled, randomized study, conducted during a 2.5-yr period, comparing the two treatment protocols.. General ICU of a university-affiliated municipal hospital.. Sixty consecutive critically ill patients with confirmed or suspected Candida infection.. Patients received amphotericin B (1 mg/kg/24 hrs), administered randomly in 5% dextrose in water (group A), or in lipid emulsion (20% intralipid) (group B).. Clinical tolerance (fever, chills, hemodynamics), hepatorenal tolerance, and biological tolerance (serum electrolytes and coagulation profile) were evaluated. Patients receiving amphotericin B in lipid emulsion experienced a lower frequency rate of drug-associated fever (61.4% vs. 5.8%, p < .003) rigors (54% vs. 8.5%, p < .004), hypotension (17% vs. 0%), and nephrotoxicity (increase of serum creatinine concentration 66.7% vs. 20%, p < .0002). Significant (264,500 +/- 71,460 to 163,570 +/- 34,450 mm3, p < .01) thrombocytopenia, not associated with active bleeding, occurred in patients receiving amphotericin B lipid in emulsion but not in patients receiving the drug in dextrose.. Treatment with amphotericin B in a lipid emulsion when given to critically ill patients with Candida sepsis seems to be safer and as effective as the conventional mode of administration.

Topics: Adult; Aged; Amphotericin B; Candidiasis; Critical Illness; Fat Emulsions, Intravenous; Female; Glucose; Humans; Infusions, Intravenous; Intensive Care Units; Liver Function Tests; Male; Middle Aged; Prospective Studies; Renal Insufficiency; Solutions

The role of selective decontamination of the digestive tract (SDD) for the prevention of nosocomial infection in critically ill patients remains controversial, and the efficacy of this technique in patients who are already infected on presentation to the intensive care unit has not previously been assessed. We performed a double-blind randomized placebo controlled trial of SDD (parenteral cefotaxime, six-hourly oral and enteral polymyxin E, tobramycin, and amphotericin B vs placebo) for all infected patients presenting to the ICU requiring mechanical ventilation for more than 48 hours and ICU stay of more than 5 days. Daily clinical and microbiological monitoring for secondary infection was undertaken until hospital discharge. In all, 59 selective decontamination and 76 placebo fully comparable patients fulfilled criteria for enrollment and analysis (APACHE II 15.2 vs 15.1). The number of patients receiving SDD who developed nosocomial infections was significantly reduced (P = 0.048), and there were no infections caused by the enterobacteriaceae or Candida spp in this group. No difference in ICU (17.5 vs 18.8 days) or hospital stay (32.7 vs 34.2 days) or mortality (17% vs 22.3%) was shown. Critically ill, primarily infected patients are protected from nosocomial infection by the use of SDD.

Topics: Administration, Oral; Adult; Amphotericin B; Cefotaxime; Colistin; Critical Care; Critical Illness; Cross Infection; Digestive System; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Placebos; Prospective Studies; Respiration, Artificial; Survival Rate; Tobramycin

The significance of candiduria in critically ill patients remains unclear. It may represent harmless colonization or a potentially life-threatening infection. We analyzed 47 patients in the surgical intensive care unit (SICU) (trauma: 20, general surgery: 15, neurosurgery: 12) who had candiduria, defined by a colony count greater than 100,000/mL. Twenty-seven of these patients were studied retrospectively. Twenty were evaluated prospectively. All patients were receiving broad-spectrum antibiotics for bacterial infections. Retrospective group: ten patients (group A) did not develop disseminated candidiasis, whereas 17 patients (group B) did. Group B had higher APACHE II scores on admission (13.4 +/- 7.8) and at the time of candiduria (13.7 +/- 4.4) when compared with group A [admission: 5.0 +/- 4.6; candiduria: 6.7 +/- 3.6 (p < 0.02)]. In group B, disseminated candidiasis was not diagnosed and treated until 9.9 +/- 4.4 days after development of candiduria. Prospective group: twenty patients with candiduria were treated with systemic fluconazole (group C) at the time of candiduria. The APACHE II scores of group C on admission (12.8 +/- 3.9) and at the time of candiduria (10.5 +/- 4.0) were comparable with those of group B. No patient in Group C developed disseminated candidiasis. The septic mortality rates of groups A, B, and C were 0%, 53%, and 5%, respectively (p < 0.05-0.0001). In patients exhibiting ongoing sepsis and organ failure (high APACHE scores), candiduria may be an early indicator of systemic infection. Diagnosis of disseminated infection and its treatment may be delayed if conventional criteria for candidiasis (positive blood cultures, multiple site isolation) are awaited.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Amphotericin B; Bacterial Infections; Candidiasis; Cause of Death; Colony Count, Microbial; Critical Illness; Cross Infection; Fluconazole; Fungemia; Hospital Mortality; Humans; Infection Control; Infusions, Intravenous; Middle Aged; Prospective Studies; Retrospective Studies; Risk Factors; Severity of Illness Index; Superinfection; Therapeutic Irrigation; Urinary Tract Infections; Urine

Topics: Amphotericin B; Critical Illness; Humans; Intraabdominal Infections; Propensity Score; Renal Insufficiency; Retrospective Studies; Sepsis

Coronavirus disease 2019 (COVID-19), which is attributable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been causing a worldwide health issue. Airways colonization by Candida spp. is prevalent among patients on automatic ventilation in intensive care units (ICUs). This research aimed to ascertain the risk factors and roles of Candida spp. respiratory tract colonization, and Candida lung infection during the progression of COVID-19 pneumonia in critically ill patients. In total, Candida spp. were recovered in 69 from 100 immunosuppressed patients with COVID-19. Bronchoscopy was used to collect the Bronchoalveolar lavage (BAL) specimens. For the identification of Candida spp. PCR sequencing was done using the ITS1 and ITS4 primers. The amplification of the HWP1 gene was conducted to identify the Candida albicans complex. The antifungal activities of fluconazole, itraconazole, voriconazole, amphotericin B and caspofungin against Candida spp. were evaluated using the Clinical and Laboratory Standards Institute M60. In 63.77% of the patients, Candida respiratory colonization at D0 and D14 had no impact on the severity of COVID-19. In comparison to C. albicans strains, Candida respiratory disorder with C. glabrata had influenced the severity of COVID-19 for critically ill patients following adjustment for the risk factors of COVID-19 (P < 0.05). Amphotericin B and caspofungin showed superior activity against all Candida spp. All antifungal agents showed 100% sensitivity against the two C. africana strains. Our observation on patients who used automatic ventilation, respiratory colonization by Candida spp. was not seen to influence the infection or death caused by COVID-19. Amphotericin B and caspofungin showed superior activity against all Candida spp. and were recommended for the treatment regime of pulmonary candidiasis associated with COVID-19 infection. Although "Candida pneumonia" is rarely being reported in critically ill patients, Candida airway colonization mainly by Candida albicans is common especially among patients with diabetes, malignancies, and kidney disorders.

Topics: Amphotericin B; Antifungal Agents; Candida; Candida albicans; Candida glabrata; Candidiasis; Caspofungin; COVID-19; Critical Illness; Fluconazole; Humans; Lung; Microbial Sensitivity Tests; Pneumonia; SARS-CoV-2

Topics: Amphotericin B; Antifungal Agents; COVID-19; Critical Illness; Drug Monitoring; Humans; Immunoassay; Polyenes

The aim of the study was to investigate the Candida species distribution and their antifungal sensitivities, clinical characteristics, and risk factors of the critically ill patients with invasive Candida infections in a tertiary hospital.. Candida strains from critically ill patients were isolated in a tertiary hospital of Anhui Province from June 2019 to June 2020 through fungal cultures and identified with MALDI-TOF MS system. The antifungal susceptibility was measured by ATB Fungus-3 method. Demographic information and laboratory data were retrieved from the computerized hospital data system.. Candida albicans (C. albicans, 41.49%) was the predominant species in sterile body sites of critically ill patients developing invasive candidiasis, followed by C. glabrata (24.47%) and C. tropicalis (20.21%). The specimen sources were mainly urine (47.87%), then bronchoalveolar lavage fluid (18.09%) and blood (14.89%). In vitro, common Candida species were observed to be highly sensitive to amphotericin B and 5-fluorocytosine. All C. albicans exhibited susceptibility to both fluconazole and voriconazole, as did C. glabrata and C. parapsilosis. However, some C. tropicalis identified were frequently resistant to fluconazole, itraconazole, and voriconazole. The rate of Candida infection was positively correlated with certain risk factors including invasive interventions, age, length of stay in hospital, etc. Conclusions: C. albicans was the main species of invasive Candida infections in critically ill patients, followed by C. glabrata and C. tropicalis. Candida spp. showed the highest rate (10.60%) of resistance to fluconazole, followed by itraconazole (5.30%), voriconazole (5.30%), and 5-fluorocytosine (1.10%). All invasive Candida isolates were sensitive to amphotericin B. In addition, several C. tropicalis were tested and exhibited a high-level resistance to azoles. Notably, a variety of specific risk factors for candidiasis were identified in critically ill patients which need to be taken into consideration.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Candidiasis, Invasive; Critical Illness; Drug Resistance, Fungal; Fluconazole; Flucytosine; Humans; Itraconazole; Microbial Sensitivity Tests; Risk Factors; Voriconazole

Topics: Amphotericin B; Communicable Diseases; Critical Illness; Humans; Intraabdominal Infections; Propensity Score; Renal Insufficiency; Retrospective Studies; Sepsis

Liposomal amphotericin B (L-AmB) is a broad-spectrum antifungal drug. Little is known about its pharmacokinetics (PK) in critically ill patients. The aim of this study was to document the PK of L-AmB in this population. It was also explored if covariates may be identified that influence its exposure. All adult, critically ill patients (at the intensive care unit or hematology ward) treated with L-AmB between October 2016 and January 2020 were eligible for this study. The administered dose was left at the discretion of the treating clinician. Plasma samples were collected at predose and 1, 2, 4, 8, 12, 16, 20 and 24 h postdose at an early (day 2-3) and/or later (≥ day 6) treatment day. Additionally, daily trough concentrations were collected until day 14. Of 33 included patients, 31 were evaluable; their median [IQR] age and body weight was 59 [54-64] years and 68 [59-77] kg, respectively. L-AmB was administered at doses between 2.7 mg/kg and 12.3 mg/kg, with a median [IQR] trough concentration of 3.1 [2.0-4.7] mg/l. The overall median area under the 24 h concentration-time curve (AUC0-24) and peak plasma concentration (Cmax) were 169.0 [117.0-253.0] mg h/l and 23.2 [16.9-33.7] mg/l, respectively. A considerable intra- and interpatient PK variability for Cmax and AUC0-24 was observed but no explaining variables, except the administered dose, could be identified. The PK of L-AmB in critically ill patients was documented. A considerable variability in exposure was observed between and within patients; however, it was not associated with a multitude of patient-related characteristics.. L-AmB is marketed for decades to treat invasive fungal infections; however, not much is known about its exposure. We documented L-AmB exposure in 31 critically ill patients. Although median exposure was similar compared to noncritically ill patients, a considerable variability was observed.

Topics: Amphotericin B; Animals; Antifungal Agents; Critical Illness; Prospective Studies

Continuous infusion of conventional amphotericin B (CCAB) is used in ICUs for pre-emptive treatment of invasive fungal infections. Amphotericin B has previously been associated with nephrotoxicity.. To investigate if CCAB with therapeutic drug monitoring (TDM) results in renal impairment over time in critically ill patients with abdominal sepsis.. The study was conducted at mixed medical-surgical ICUs of two large teaching hospitals in the Netherlands. Consecutive patients who were treated on the ICUs between 2006 and 2019 for abdominal sepsis, with or without CCAB, were included. CCAB dosing was guided by TDM. Serum creatinine concentrations and renal failure scores of patients with CCAB treatment were compared with those without CCAB treatment. Excluded were: (i) patients treated with CCAB for less than 72 h; and (ii) patients with renal replacement therapy.. A total of 319 patients were included (185 treated with CCAB and 134 controls). A multiple linear regression model showed that the serum creatinine concentration was independent of CCAB treatment (β = -0.023; 95% CI = -12.2 to 7.2; P = 0.615). Propensity score matching resulted in 134 pairs of CCAB-treated and non-treated patients. Again, the analysis of these pairs showed that the cumulative CCAB dose was not associated with serum creatinine concentration during intensive care treatment (β = 0.299; 95% CI = -0.38 to 0.98; P = 0.388).. CCAB with TDM did not result in renal impairment over time in critically ill patients with abdominal sepsis.

Topics: Amphotericin B; Critical Illness; Humans; Propensity Score; Renal Insufficiency; Retrospective Studies; Sepsis

Topics: Amphotericin B; Candidiasis, Invasive; Critical Illness; Humans

Topics: Amphotericin B; Candida; Candidiasis, Invasive; Critical Illness; Humans

Topics: Amphotericin B; Antifungal Agents; Critical Illness; Deoxycholic Acid; Drug Combinations; Humans

Critically ill patients are at risk of developing both acute kidney injury (AKI) and invasive fungal infections (IFIs). Prompt and efficient treatment of the IFI is essential for the survival of the patient. This article examines three distinct clinical situations where liposomal amphotericin B, a broad-spectrum antifungal agent, was successfully used in the setting of AKI. The first was

Topics: Acute Kidney Injury; Adult; Aged; Amphotericin B; Antifungal Agents; Critical Illness; Female; Humans; Invasive Fungal Infections; Male; Middle Aged

Histoplasmosis is a systemic mycosis caused by the dimorphic fungus Histoplasma capsulatum, with disseminated histoplasmosis (HD) being one of its clinical forms. As a consequence of the HIV-AIDS pandemic, HD has become prevalent not only in regions that are recognized as endemic but also in areas not considered endemic, such as Europe and Asia. Its clinical manifestations are varied and mimic several infectious diseases, mainly tuberculosis. In endemic areas, it is the first manifestation of AIDS in 50 to 70% of patients. The diagnosis of histoplasmosis is difficult and HD can lead to death if not diagnosed early and if proper treatment is not instituted. The present report presents a patient with a recent diagnosis of HIV-AIDS, in treatment for miliary tuberculosis, who was diagnosed with disseminated histoplasmosis because of his dermatological manifestations.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Anti-HIV Agents; Antifungal Agents; Antitubercular Agents; Critical Illness; Dermatomycoses; Histoplasma; Histoplasmosis; Humans; Itraconazole; Male; Tuberculosis, Miliary; Young Adult

We describe the use of liposomal amphotericin B and amphotericin B deoxycholate in a critically ill patient with pulmonary blastomycosis receiving both venovenous extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT).. A 50-year-old African American man presented for dyspnea and cough and was noted to have blastomycosis on bronchoscopy. He developed respiratory failure and acute kidney injury, requiring mechanical ventilation, ECMO, and CRRT. After 4 days of liposomal amphotericin, the transmembrane pressure gradient on the membrane oxygenator increased dramatically without visualization of a clot, requiring a circuit exchange. A trough amphotericin B level taken the day before the exchange was undetectable for amphotericin B. After the circuit exchange, the patient was switched to amphotericin B deoxycholate. A subsequent trough level was 3.8 μg/mL. The patient improved and was able to be decannulated. However, he did require tracheostomy and long-term hemodialysis.. In our case we believe that liposomal amphotericin B was significantly removed by ECMO and was responsible for the failure of the ECMO circuit. We would suggest amphotericin B deoxycholate be used in such patients preferentially and that serum levels of the drug be assessed when possible.

Topics: Acute Kidney Injury; Amphotericin B; Area Under Curve; Blastomycosis; Combined Modality Therapy; Continuous Renal Replacement Therapy; Critical Illness; Deoxycholic Acid; Drug Combinations; Drug Substitution; Equipment Failure; Extracorporeal Membrane Oxygenation; Humans; Male; Middle Aged; Oxygenators, Membrane; Respiratory Insufficiency; Treatment Outcome

To identify the incidence, risk factors and impact on long-term survival of invasive pulmonary aspergillosis (IPA) and Aspergillus colonisation in patients receiving vv-extracorporeal membrane oxygenation (ECMO). A retrospective evaluation was performed of patients receiving vv-ECMO at a tertiary hospital in Manchester (UK) between January 2012 and December 2016. Data collected included epidemiological data, microbiological cultures, radiographic findings and outcomes. Cases were classified as proven IPA, putative IPA or Aspergillus colonisation according to a validated clinical algorithm. One hundred thirty-four patients were supported with vv-ECMO, median age of 45.5 years (range 16.4-73.4). Ten (7%) patients had putative IPA and nine (7%) had Aspergillus colonisation. Half of the patients with putative IPA lacked classical host risk factors for IPA. The median number of days on ECMO prior to Aspergillus isolation was 5 days. Immunosuppression and influenza A infection were significantly associated with developing IPA in a logistic regression model. Cox regression model demonstrates a three times greater hazard of death associated with IPA. Overall 6-month mortality rate was 38%. Patients with putative IPA and colonised patients had a 6-month mortality rate of 80 and 11%, respectively. Immunosuppression and influenza A infection are independent risk factors for IPA. IPA, but not Aspergillus colonisation, is associated with high long-term mortality in patients supported with vv-ECMO.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Aspergillus; Critical Illness; Echinocandins; Extracorporeal Membrane Oxygenation; Female; Galactose; Humans; Immunocompromised Host; Influenza, Human; Invasive Pulmonary Aspergillosis; Lipopeptides; Male; Mannans; Micafungin; Middle Aged; Retrospective Studies; Risk Factors; Treatment Outcome; Voriconazole; Young Adult

Invasive aspergillosis(IA) is a potentially lethal complication of Aspergillus infection affecting mainly immunocompromised hosts; however, during the last two decades its incidence was increasingly observed in critically ill immunocompetent patients. The objective of this study is to describe the clinical characteristics of histologically proven endomyocardial and pericardial invasion, in the context of IA, in critically ill patients. Eight critically ill patients with histopathological confirmation of endomyocardial/pericardial aspergillosis were evaluated. Risk factors, clinical and laboratory characteristics, treatment, histopathological characteristics and mortality were recorded. Signs and symptoms of cardiac dysfunction were not observed in any of the patients. Therapy was administered to six of them shortly after the first positive culture. The observed histopathological lesions included haemorrhagic lesions, small vessels with central thrombosis and surrounding consolidated tissue with necrosis. Voriconazole, caspofungin, lipid amphotericin B and itraconazole were the used antifungals. The mortality rate was high (87.5%). Endomyocardial and pericardial aspergillosis are devastating complications of invasive aspergillosis. Clinical suspicion is low making the diagnosis difficult, therefore histopathological examination of tissues are required. The mortality is high.

Topics: Amphotericin B; Antifungal Agents; Caspofungin; Critical Illness; Echinocandins; Female; Heart Diseases; Humans; Immunocompetence; Immunocompromised Host; Incidence; Invasive Fungal Infections; Lipopeptides; Male; Middle Aged; Myocardium; Pericardium; Risk Factors; Voriconazole

To demonstrate the feasibility and safety of weekly high-dose liposomal amphotericin B (L-AmB) (as a pre-emptive antifungal treatment) for 2 weeks in patients with septic shock and Candida colonization.. Pilot, multicentre, open-label, prospective study conducted in seven French ICUs. Non-immunocompromised patients, receiving mechanical ventilation were eligible if they presented ICU-acquired severe sepsis requiring newly administered antibacterial agents and Candida colonization in at least two sites. Exclusion criteria included the need for antifungal therapy and creatinine > 220 μmol/L. All patients were to receive a high-dose L-AmB (10 mg/kg/week) for two weeks. A follow-up period of 21 days following the second administration of L-AmB was conducted. Treated patients were compared to 69 matched untreated controls admitted in the same ICUs before the study period.. Twenty-one patients were included in the study, of which 20 received at least one infusion of high-dose L-AmB. A total of 24 adverse events were identified in 13(61%) patients. Fourteen adverse events were categorized as serious in 8(38%) patients. In four cases the adverse events were considered as potentially related to study drug administration and resulted in L-AmB discontinuation in one patient. Few patients experienced severe renal toxicity since no patient presented with severe hypokalemia. No patients required renal replacement therapy. Compared to matched controls, no significant increase in serum creatinine levels in patients receiving high-dose L-AmB was reported.. Weekly administration of high-dose L-AmB has a manageable safety profile and is feasible in patients with ICU-acquired sepsis and multiple Candida colonization. Trials of L-AmB versus other antifungal agents used as pre-emptive antifungal therapy are warranted.. ClinicalTrials.gov NCT00697944.

Topics: Aged; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Critical Illness; Cross Infection; Female; Humans; Intensive Care Units; Male; Middle Aged; Pilot Projects; Prospective Studies; Sepsis; Treatment Outcome

Invasive pulmonary aspergillosis (IPA) is an increasingly recognised problem in critically ill patients. Little is known about how intensivists react to an Aspergillus-positive respiratory sample or the efficacy of antifungal therapy (AFT). This study aimed to identify drivers of AFT prescription and diagnostic workup in patients with Aspergillus isolation in respiratory specimens as well as the impact of AFT in these patients. ICU patients with an Aspergillus-positive respiratory sample from the database of a previous observational, multicentre study were analysed. Cases were classified as proven/putative IPA or Aspergillus colonisation. Demographic, microbiological, diagnostic and therapeutic data were collected. Outcome was recorded 12 weeks after Aspergillus isolation. Patients with putative/proven IPA were more likely to receive AFT than colonised patients (78.7% vs. 25.5%; P <0.001). Patients with host factors for invasive fungal disease were more likely to receive AFT (72.5% vs. 37.4%) as were those with multiorgan failure (SOFA score >7) (68.4% vs. 36.9%) (both P <0.001). Once adjusted for disease severity, initiation of AFT did not alter the odds of survival (HR = 1.40, 95% CI 0.89-2.21). Likewise, treatment within 48 h following diagnosis did not change the clinical outcome (75.7% vs. 61.4%; P = 0.63). Treatment decisions appear to be based on diagnostic criteria and underlying disease severity at the time of Aspergillus isolation. IPA in this population has a dire prognosis and AFT is not associated with reduced mortality. This may be explained by delayed diagnosis and an often inevitable death due to advanced multiorgan failure.

Topics: Aged; Amphotericin B; Antifungal Agents; Aspergillus; Clinical Decision-Making; Critical Illness; Delayed Diagnosis; Drug Therapy, Combination; Echinocandins; Female; Fungal Proteins; Humans; Intensive Care Units; Invasive Pulmonary Aspergillosis; Male; Middle Aged; Prognosis; Respiratory System; Treatment Outcome; Voriconazole

Pseudallescheria boydii is a fungal organism known to affect immunocompromised patients. This organism is known to cause, in severe cases, invasive infection of various organs such as the central nervous, cardiovascular, and respiratory systems. We report an unusual case of pulmonary P. boydii pneumonia in an immunocompromised critically ill patient with a co-infection of Aspergillus fumigatus and Aspergillus terreus with ARDS. This case highlights the importance of a high index of suspicion for superimposed fungal infections in patients who are critically ill and immunocompromised. Uncommon fungal pathogens should be considered in the differential diagnosis of respiratory failure, especially if diagnostic markers such as galactomannan (from BAL and serum) or 1,3-beta-D-glucan are elevated. Further diagnostic interventions are warranted when insufficient clinical improvement is observed to prevent treatment failure and adverse outcomes.

Topics: Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; beta-Glucans; Clarithromycin; Coinfection; Critical Illness; Extracorporeal Membrane Oxygenation; Galactose; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Linezolid; Male; Mannans; Meropenem; Pneumonia; Pseudallescheria; Severe Acute Respiratory Syndrome; Thienamycins; Transplant Recipients; Voriconazole

Topics: Amphotericin B; Antifungal Agents; Burns; Critical Illness; Diffusion; Humans; Liposomes; Mucormycosis; Muscles; Renal Dialysis; Triazoles

Survivors of combat trauma can have long and challenging recoveries, which may be complicated by infection. Invasive fungal infections are a rare but serious complication with limited treatment options. Currently, aggressive surgical debridement is the standard of care, with antifungal agents used adjunctively with uncertain efficacy. Anecdotal evidence suggests that antifungal agents may be ineffective in the absence of surgical debridement, and studies have yet to correlate antifungal concentrations in plasma and wounds.. Here we report the systemic pharmacokinetics and wound effluent antifungal concentrations of five wounds from two male patients, aged 28 and 30 years old who sustained combat-related blast injuries in southern Afghanistan, with proven or possible invasive fungal infection. Our data demonstrate that while voriconazole sufficiently penetrated the wound resulting in detectable effluent levels, free amphotericin B (unbound to plasma) was not present in wound effluent despite sufficient concentrations in circulating plasma. In addition, considerable between-patient and within-patient variability was observed in antifungal pharmacokinetic parameters.. These data highlight the need for further studies evaluating wound penetration of commonly used antifungals and the role for therapeutic drug monitoring in providing optimal care for critically ill and injured war fighters.

Topics: Adult; Amphotericin B; Amputation, Surgical; Antifungal Agents; Aspergillosis; Blast Injuries; Burns; Critical Illness; Debridement; Drug Monitoring; Fusariosis; Humans; Male; Mucormycosis; Mycoses; Voriconazole; War-Related Injuries; Wounds, Penetrating

Fungal cholangitis is a potentially life-threatening condition. As amphotericin B (AmB) has a broad antimycotic spectrum, in this study its biliary penetration and activity was determined in two patients treated with liposomal AmB (L-AmB) and in one patient receiving AmB colloidal dispersion (ABCD). Biliary and plasma AmB levels were quantified by high-performance liquid chromatography after purification by solid-phase extraction. For assessment of biliary AmB activity, isolates of Candida albicans, Candida tropicalis, Candida glabrata and Candida krusei were incubated in porcine bile at AmB concentrations of 0.025-5.00 mg/L. In addition, patient bile samples retrieved for AmB quantification were inoculated with the same Candida strains. Biliary AmB concentrations were lower and displayed a slower rise and decline than plasma levels. The highest penetration ratio, as expressed by the ratio between the area under the AmB concentration-time curve in bile and plasma (liberated AmB) over the sampling period (AUC0-n bile/AUC0-n LI plasma), was 0.28. Proliferation of C. albicans and C. tropicalis in bile was similar to that in culture medium, whereas growth of C. glabrata was diminished and proliferation of C. krusei was absent in bile. In comparison with culture medium, AmB activity decreased in spiked porcine bile. In all but one patient bile sample, fungal growth was delayed or lacking even when AmB was not detectable. However, no fungicidal effect was observed in patient bile at AmB concentrations up to 1.28 mg/L. Thus, a reliable response of fungal cholangitis to treatment with L-AmB or ABCD cannot be anticipated.

Topics: Aged; Amphotericin B; Antifungal Agents; Biliary Tract; Candida; Critical Illness; Female; Humans; Liver Transplantation; Male; Microbial Viability; Middle Aged; Plasma; Transplant Recipients

Topics: Amphotericin B; Antifungal Agents; Candida; Critical Illness; Decontamination; Gastrointestinal Tract; Humans; Nystatin

Candida spp. are frequently cultured from the respiratory tract in critically ill patients. Most intensivists start amphotericin-B deoxycholate (ABDC) inhalation therapy to eradicate Candida spp. from the respiratory tract. However, the safety and efficacy of this treatment are not well established. The purpose of this study was to assess the safety and efficacy of ABDC inhalation for the treatment of respiratory Candida spp. colonization in critically ill patients.. All non-neutropenic patients admitted into the intensive care unit (ICU) of a university hospital from December 2010-2011, who had positive Candida spp. cultures of the respiratory tract for more than 1 day and required mechanical ventilation >48 h were retrospectively included. The decision to start ABDC inhalation had been made by attending intensivists on clinical grounds in the context of selective decontamination of the digestive tract. Infection characteristics and patient courses were assessed.. Hundred and thirteen consecutive patients were studied. Fifty-one of them received ABDC inhalation and their characteristics at baseline and day 1 of respiratory colonization did not differ from those of colonized patients not receiving treatment (n = 62). The ABDC-treated group had a similar Candida spp. load but did not decolonize more rapidly as compared to untreated patients. The clinical pulmonary infection and lung injury scores did not decrease as in the untreated group. In a Cox proportional hazard model, the duration of mechanical ventilation was increased (P < 0.003) by ABDC treatment independently of other potential determinants and Candida spp. colonization. No differences in ventilator-associated pneumonia or in overall mortality (up to day 90) were observed.. Treatment of respiratory Candida spp. colonization in non-neutropenic critically ill patients by inhaled ABDC may not affect respiratory colonization but may increase duration of mechanical ventilation, because of direct toxicity of the drug on the lung.

Topics: Administration, Inhalation; Adult; Aged; Amphotericin B; Candida; Candidiasis; Critical Illness; Deoxycholic Acid; Drug Combinations; Female; Humans; Intensive Care Units; Male; Middle Aged; Pneumonia, Ventilator-Associated; Respiration, Artificial; Respiratory Tract Infections; Retrospective Studies

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Creatinine; Critical Illness; Cross Infection; Deoxycholic Acid; Drug Combinations; Fluconazole; Humans; Intensive Care Units; Practice Patterns, Physicians'; Renal Insufficiency

The objective of this study was to examine the effect of continuous venovenous haemodiafiltration (CVVHDF) on the pharmacokinetics of amphotericin B (AmB) in critically ill patients following administration of amphotericin B lipid complex (ABLC). Plasma and ultrafiltrate (UF) samples were collected from patients administered ABLC and either receiving or not receiving CVVHDF. Pharmacokinetic (PK) analysis was performed on eight profiles from patients receiving CVVHDF and six profiles from patients not receiving CVVHDF. For patients receiving CVVHDF, the following median PK data were calculated: area under the concentration-time curve (AUC) = 13.9 h·μg/mL, volume of distribution at steady state (V(ss)) = 1476L and drug clearance (CL) = 27.4 L/h; for patients not receiving CVVHDF, the corresponding median PK data were 11.5 h μg/mL, 2048 L and 43.7 L/h, respectively. The median half-lives calculated during the dosage interval (t(1/2int)) were 30.9 h and 32.5 h on and off CVVHDF, respectively, and the total range of t(1/2int) values was 15.6-180.4 h. Observed median peak concentrations on Day 1 were 0.563 μg/mL and 0.468 μg/mL in patients on and off CVVHDF, respectively. From AmB present in the UF, clearance via CVVHDF contributed<1% of total plasma clearance. The AmB concentration-time profiles for patients administered ABLC on and off CVVHDF were compared and no statistically significant differences in AUC, CL, t(1/2int) and V(ss) were observed. In conclusion, CVVHDF had no clinically significant effect on the pharmacokinetics of AmB following administration of ABLC.

Topics: Aged; Amphotericin B; Antifungal Agents; Area Under Curve; Critical Illness; Female; Half-Life; Hemodiafiltration; Humans; Male; Middle Aged; Plasma

Colonisation of the lower respiratory tract with Candida species occurs in 25% of mechanically ventilated critically ill patients, and is associated with increased morbidity. Nebulised amphotericin B has been used to eradicate Candida as part of selective decontamination of the digestive tract (SDD) protocols, but its effectiveness is unknown. We aimed to determine the effectiveness of nebulised amphotericin B in eradicating Candida respiratory tract colonisation in patients receiving SDD.. We included consecutive mechanically ventilated patients during a four-year period. Microbiological screening was performed upon admission and twice weekly thereafter according to a standardised protocol. A colonisation episode was defined as the presence of Candida species in two consecutive sputum samples taken at least one day apart. To correct for time-varying bias and possible confounding, we used a multistate approach and performed time-varying Cox regression with adjustment for age, disease severity, Candida load at baseline and concurrent corticosteroid use.. Among 1,819 patients, colonisation with Candida occurred 401 times in 363 patients; 333 of these events were included for analysis. Decolonisation occurred in 51 of 59 episodes (86%) and in 170 of 274 episodes (62%) in patients receiving and not receiving nebulised amphotericin B, respectively. Nebulised amphotericin B was associated with an increased rate of Candida eradication (crude HR 2.0; 95% CI 1.4 to 2.7, adjusted HR 2.2; 95% CI 1.6 to 3.0). Median times to decolonisation were six and nine days, respectively. The incidence rate of ventilator-associated pneumonia, length of stay and mortality did not differ between both groups.. Nebulised amphotericin B reduces the duration of Candida colonisation in the lower respiratory tracts of mechanically ventilated critically ill patients receiving SDD, but data remain lacking that this is associated with a meaningful improvement in clinical outcomes. Until more evidence becomes available, nebulised amphotericin B should not be used routinely as part of the SDD protocol.

Topics: Administration, Inhalation; Adult; Aged; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Critical Illness; Decontamination; Digestive System; Female; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Netherlands; Pneumonia, Ventilator-Associated; Respiratory System

This study was designed to compare the effectiveness of liposomal amphotericin B (L-AmB) in ICU patients with and without renal replacement therapy (RRT).. Observational, retrospective, comparative and multicenter study conducted in critically ill patients treated with L-AmB for 3 or more days, divided into two cohorts depending on the use of RRT before or within the first 48 hours after starting L-AmB. Clinical and microbiological response at the end of treatment was evaluated.. A total of 158 patients met the inclusion criteria, 36 (22.8%) of which required RRT during the ICU stay. Patients with RRT as compared with those without RRT showed a higher APACHE II score on admission (21.4 vs 18.4, P = 0.041), greater systemic response against infection (P = 0.047) and higher need of supportive techniques (P = 0.002). In both groups, main reasons for the use of L-AmB were broad spectrum and hemodynamic instability. A higher daily dose of L-AmB was used in the RRT group (4.30 vs 3.84 mg/kg, P = 0.030) without differences in the total cumulative dose or treatment duration. There were no differences in the clinical response (61.1% vs 56.6%, P = 0.953) or microbiological eradication rate (74.1% vs 64.6%, P = 0.382). In patients with proven invasive fungal infection, satisfactory clinical response was obtained in 74.1% and microbiological eradication 85.7%.. Although the study sample is small, this study shows that L-AmB is effective in critically ill patients admitted to the ICU requiring RRT.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; APACHE; Bacterial Infections; Cohort Studies; Critical Illness; Female; Hemodynamics; Hospital Mortality; Humans; Kidney Diseases; Length of Stay; Male; Middle Aged; Prospective Studies; Renal Replacement Therapy; Spain; Treatment Outcome

There are limited data about the use of antifungal agents (AF) in critically ill patients and treatment trends since the inclusion of the new generation AF. The use of these agents may have a significant influence on the development of new resistances.. Observational prospective study of the systemic use of AF in patients admitted to Spanish intensive care units (ICU) participating in the ENVIN-HELICS register, from 2006 to 2010. The annual use, the indications that led to that use and, the intra-ICU infections, the AF employment related to the hospital size, and per 1000 patients/day, were compared.. Of the 8240 prescriptions for AF, fluconazole and caspofungin were the most often employed (55% and 19.5%, respectively). An increase in use was observed to the year 2008, with subsequent stabilisation. A decrease in the use of fluconazole and an increase in echinocandins consumption was observed over time. As regards the intra-ICU infections, the AF were ordered empirically in 47.9% of the indications. Fluconazole was more frequently used in medium size hospitals than in the large ones (60.4% versus 53.3%; P=.036) and the opposite occurred in the case of caspofungin (15.8% versus 21.8%; P<.001). Fluconazole was more prematurely employed (median 12 days since ICU admission) and the duration of the therapy was similar to the other AF (median 8 days). The total therapy days were 39.51 per 1000 patient/day, with predominance in fluconazole use (21.48 per 1000 patients/day).. Fluconazole is the most used antifungal agent in critically ill patients in any of the indications, although a progressive decrease in its use is observed, with a proportional increase in the use of echinocandins.

Topics: Amphotericin B; Antifungal Agents; Caspofungin; Community-Acquired Infections; Critical Illness; Cross Infection; Drug Prescriptions; Drug Utilization; Echinocandins; Female; Fluconazole; Hospital Bed Capacity; Humans; Immunocompromised Host; Intensive Care Units; Lipopeptides; Male; Middle Aged; Mycoses; Neutropenia; Prospective Studies; Registries; Spain

The pharmacokinetics of lipid-bound and liberated amphotericin B (AMB) was assessed in 11 critically ill patients with cholestatic liver disease (CSLD) and in 9 subjects with normal liver function treated with AMB colloidal dispersion (ABCD). Exposure to lipid-bound AMB was higher in patients with CSLD. Levels of liberated AMB were elevated by CSLD only after the first dose, whereas its pharmacokinetics was unaffected at steady state. The standard dosage of ABCD is probably adequate for patients with CSLD.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Child; Colloids; Critical Illness; Female; Humans; Liver Diseases; Male; Middle Aged; Young Adult

To assess the tolerability of liposomal amphotericin B (L-AmB) in critically ill patients with elevated serum creatinine concentrations (Cr) (> 1.5 mg/dL) at starting L-AmB therapy.. Retrospective, multicenter, comparative study of two cohorts of critically ill patients treated with L-AmB during 3 or more days, the difference between them was the level of Cr at the beginning of treatment. A cutoff value of Cr of 1.5 mg/dL was established. Patients undergoing extrarenal depuration procedures before or 48 hours after starting L-AmB were excluded. The primary endpoint was the difference between Cr values at the end of treatment as compared with Cr at starting L-AmB. Secondary endpoints were treatment-related withdrawals, need of extrarenal depuration techniques, and treatment-related severe adverse events. Demographic data, underlying illness, indication of L-AmB therapy, concomitant risk factors of nephrotoxicity, and vital status at ICU and hospital discharge were recorded.. A total of 122 patients admitted to 26 ICUs (16 with Cr > 1.5 g/dL; 106 with normal Cr levels) were recruited. Main reasons for the use of L-AmB in both groups were the broad spectrum of the drug and the presence of hemodynamic instability. L-AmB was administered as first-line treatment in 68.8% of patients with elevated Cr and in 52.8% with normal Cr. The APACHE II score on ICU admission was 25 in patients with elevated Cr and 17 in those with normal Cr values (p < 0.001). Duration of treatment with L-AmB was 16 and 12 days in patients with elevate and normal Cr values, respectively, with a mean dose of 3.5 vs 3.9 mg/kg/day. The use of concomitant nephrotoxic drugs, mortality rate, and ICU and hospital length of stay were similar in both cohorts. In patients with renal function impairment at the initiation of L-AmB treatment, an absolute decrease of Cf-Ci of 1.08 mg/dL was observed (P < 0.001). A decrease of Cr levels to normal limits was observed in 50% of the patients; in 37.5% of patients there was a decrease but normal levels were not achieved, whereas a Cr increased occurred in only one (6.25%) patient. None of the patients required withdrawal of L-AmB or use of extrarenal depuration procedures. Treatment-related severe adverse events were not reported.. In critically ill patients with impaired renal function, the impact of L-AmB on renal function was minimal. L-AmB can be used for the treatment of fungal infections in critically ill patients independently of renal function at the initiation of treatment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Cohort Studies; Creatinine; Critical Illness; Female; Humans; Infant; Kidney; Kidney Diseases; Kidney Function Tests; Male; Middle Aged; Mycoses; Retrospective Studies; Young Adult

In the present work, we studied the distribution of Candida parapsilosis complex species and the antifungal susceptibility of clinical isolates collected during an Italian surveillance study of yeast invasive fungal infections (IFIs) in intensive care units (ICUs). Minimum inhibitory concentrations (MICs) were determined using the Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution method. BanI digestion patterns of the secondary alcohol dehydrogenase polymerase chain reaction (PCR) products were used to identify C. parapsilosis sensu stricto, C. orthopsilosis, and C. metapsilosis. A total of 138 C. parapsilosis isolates were stored (January 2007-December 2008). The overall frequency of C. parapsilosis complex in IFIs was 22%. Of the 138 tested isolates, 95% were C. parapsilosis sensu stricto, 3.6% were C. orthopsilosis, and 1.4% were C. metapsilosis. The MIC(50) values (expressed as μg/ml) for anidulafungin, caspofungin, and micafungin for C. parapsilosis complex were 2, 1, and 2, respectively, and the MIC(90) values were 4, 2, and 4, respectively. The MIC(50) and MIC(90) values for itraconazole and posaconazole were 0.12 and 0.25, respectively, and for fluconazole, they were 1 and 4, respectively. This study, the most comprehensive study conducted to date to evaluate the frequency and antifungal susceptibility profiles of C. parapsilosis complex isolates from critically ill patients in Italy, highlights the low prevalence of C. orthopsilosis and C. metapsilosis in IFIs.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alcohol Dehydrogenase; Amphotericin B; Antifungal Agents; Candida; Candidiasis, Invasive; Child; Child, Preschool; Critical Illness; Echinocandins; Fungal Proteins; Humans; Infant; Infant, Newborn; Intensive Care Units; Italy; Microbial Sensitivity Tests; Middle Aged; Mycological Typing Techniques; Polymerase Chain Reaction; Triazoles; Young Adult

Albumin dialysis (AD) is a therapeutic option in severe cholestatic liver failure. However, it can significantly enhance drug elimination. Pharmacokinetic data on antimicrobial agents--in particular on antimycotics--administered under this clinical condition are very sparse. Therefore, amphotericin B (AMB) plasma concentrations were measured in two critically ill patients who were treated with AD because of severe cholestatic liver failure and were prescribed lipid formulated AMB--either AMB colloidal dispersion (ABCD) or AMB lipid complex (ABLC)--for suspected invasive fungal infection. AD was performed with the molecular adsorbent recirculating system (MARS). Lipid-associated and liberated AMB were separately quantified on and off AD. The clearance of the liberated AMB fraction was not essentially affected (ABLC) or moderately enhanced during AD by a factor of 2.5 (ABCD). The clearance of the lipid-formulated fraction was increased by a factor of 4 during AD (ABCD) or was similar (ABLC) on and off AD. Despite the fact that there was a four-fold higher clearance of the lipid-formulated fraction of ABCD, the clinically relevant area under the concentration time curve of the liberated AMB fraction was only moderately changed (by 37% in ABCD, 70% in ABLC) during AD. Thus, the effect of AD on lipid formulated AMB appears to be moderate. A daily dose of 5 mg/kg will probably lead to adequate plasma levels in patients on AD.

Topics: Aged; Albumins; Amphotericin B; Antifungal Agents; Critical Illness; Female; Humans; Lipid Metabolism; Liver Failure; Male; Middle Aged; Mycoses; Renal Dialysis

The clinical use of liposomal amphotericin B in 179 patients admitted to 30 medical-surgical intensive Care Units (ICUs) treated with this agent in 2006 was analyzed. Invasive fungal infections were proven, probable and possible in 44%, 16%, and 25% of cases, respectively. Fungi isolated were Candida albicans (38%), non-albicans Candida spp. (15%) and Aspergillus spp. (7%). The mean duration of treatment was 15 days (mean dose 3.7 mg/kg/day). The drug was used as rescue treatment after fluconazole or caspofungin in 47% of patients and as first line in 52% with a satisfactory clinical response in 54% of cases (72.6% with proven infection). Microbiological eradication was achieved in 68% of cases. Adverse events occurred in 51 patients but were severe in only 4. The use of liposomal amphotericin B both as first line and rescue treatment and mainly for proven invasive fungal infection was associated with a high rate of satisfactory clinical response.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; APACHE; Critical Illness; Female; Humans; Intensive Care Units; Male; Middle Aged; Mycoses; Retrospective Studies

Selective decontamination of the digestive tract (SDD) decreases morbidity and mortality in critically ill patients and morbidity in patients undergoing esophageal resection. This study analyzes the effect of perioperative SDD in patients undergoing elective colorectal surgery on postoperative infections and anastomotic leakage.. This is a retrospective analysis of prospectively collected data in a 3-year cohort of 162 patients undergoing elective resection of colon and or rectum. Of these patients, 76 (47%) received SDD (polymyxine B sulfate, tobramycin, and amphotericin) perioperatively. The control group consisted of 86 patients who were not treated with SDD. Postoperative complications, hospital stay, and mortality were analyzed.. In the SDD group, there were six patients (7.9%) with infectious complications compared with 17 patients (19.8%) in the control group (p = 0.031). The incidence of the combined endpoint infectious complications and anastomotic leakage was 8 (11%) in the SDD group vs. 22 (26%) in the control group (p = 0.014). Multivariate analysis showed that no-SDD, aged above 60 years and diabetes were independent predictors of postoperative complications.. Perioperative SDD in elective colorectal surgery seems to reduce postoperative surgical complications including infectious complications and anastomotic leakage. Prospective, randomized, placebo-controlled studies are needed to confirm this conclusion.

Topics: Aged; Amphotericin B; Anastomosis, Surgical; Anti-Bacterial Agents; Antibiotic Prophylaxis; Colectomy; Colon; Critical Illness; Digestive System Surgical Procedures; Elective Surgical Procedures; Female; Humans; Infection Control; Male; Middle Aged; Polymyxin B; Postoperative Complications; Rectum; Retrospective Studies; Tobramycin

Topics: Adult; Aged; Amphotericin B; Ascitic Fluid; Critical Illness; Humans; Male; Middle Aged

To report a case of fungal sepsis treated prospectively with liposomal amphotericin, caspofungin, and a novel monoclonal antibody specific for candidal heat shock protein 90 (Mycograb, Neutec Pharma, Manchester, UK).. Case report.. Pediatric intensive care unit in a tertiary care children's hospital.. A 7-yr-old male with a history of global developmental delay, epilepsy, and gastroesophageal reflux, who presented to the emergency department with a transdiaphragmatic herniation of bowel and subsequent Candida glabrata infection.. Efungumab 1 mg/kg twice daily for 5 days.. C-reactive protein fell from 225 mg/L to 99 mg/L, and physiological monitoring parameters improved when Mycograb was used in conjunction with high-dose antifungals.. Mycograb therapy was well tolerated, but further experience with this therapy in children is needed.

Topics: Amphotericin B; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antifungal Agents; Candida glabrata; Candidiasis; Caspofungin; Child; Critical Illness; Drug Therapy, Combination; Echinocandins; Hernia, Diaphragmatic; HSP90 Heat-Shock Proteins; Humans; Lipopeptides; Male; Postoperative Complications; Recombinant Proteins; Sepsis

Tracheotomy is considered to be an independent risk factor for ventilator-associated pneumonia (VAP). Antimicrobial prophylaxis, in particular with coverage of Pseudomonas aeruginosa, is presently advocated. Selective decontamination of the digestive tract (SDD) aims to prevent VAP in critically ill patients, including those after tracheotomy. We determined the incidence and microbial spectrum of VAP after tracheotomy in a SDD-setting.. Retrospective analysis of 231 tracheotomized patients during a 2-year period.. Thirteen patients (5.6%) developed VAP. The median [IQR] day of onset was 8.0 [3.0-10.5] days after tracheotomy. The most predominant causative pathogen was Methicillin-sensitive Staphylococcus aureus (MSSA). Timing of tracheotomy was not different between patients developing VAP and those who did not. The type of tracheotomy (percutaneous or surgical, 84.6% versus 15.4%) had no significant influence on the incidence of VAP.. The incidence of VAP after tracheotomy in a SDD-setting is low, with MSSA as the predominant causative pathogen. Accordingly, if antimicrobial prophylaxis is considered, it may be advisable to cover MSSA in an SDD-setting.

Topics: Administration, Buccal; Adult; Aged; Amphotericin B; Anti-Bacterial Agents; Antibiotic Prophylaxis; Colistin; Critical Illness; Cross Infection; Decontamination; Enteral Nutrition; Female; Gastrointestinal Tract; Humans; Incidence; Intensive Care Units; Male; Methicillin; Microbial Sensitivity Tests; Middle Aged; Netherlands; Pneumonia, Ventilator-Associated; Retrospective Studies; Risk Factors; Staphylococcus aureus; Tobramycin; Tracheotomy

To determine the efficacy of oral amphotericin B for the prevention of Candida bloodstream infection in the pediatric intensive care unit.. Retrospective, nonrandomized, historic-control study.. Multidisciplinary pediatric intensive care unit at a university-affiliated children's medical center.. Study group included all patients admitted to the pediatric intensive care unit from January 1, 1998, to December 31, 1999, who required mechanical ventilation and who were admitted for >7 days. The control group included all patients admitted for >7 days who needed mechanical ventilation from January 1, 1994, to December 31, 1997.. Oral amphotericin B suspension, 50 mg every 8 hrs, administered to all study group patients soon after initiation of mechanical ventilation and terminating after weaning.. The rates of Candida bloodstream infection were compared between the study and control groups.. Candida species were isolated from blood cultures in 5 of 185 (2.1%) and 21 of 196 (10.7%) patients in the study and control groups, respectively (p= .0038). There was also a statistically significant (p= .017) decrease in Candida bloodstream infection rate in all patients admitted to the pediatric intensive care unit for >7 days during the study period compared with the Candida bloodstream infection rate during the control period.. Prophylactic administration of oral amphotericin B may lead to a significant decrease in the rate of Candida bloodstream infection in ventilated pediatric intensive care unit patients.

Topics: Administration, Oral; Amphotericin B; Antifungal Agents; Candidiasis; Child; Critical Illness; Cross Infection; Fungemia; Humans; Intensive Care Units, Pediatric; Respiration, Artificial; Retrospective Studies

Consecutive Candida glabrata isolates recovered from a patient in an intensive care unit were resistant to amphotericin B (minimum inhibitory concentration, up to 32 mu g/mL; determined by Etest [AB Biodisk]). Analyses at the national reference laboratory showed that some isolates were also resistant to azoles and caspofungin. In this study, 4 isolates were studied thoroughly using susceptibility assays and a mouse model and to determine clonality.. Different broth microdilution tests, Etests, and time-kill studies for antifungals were performed in different media. Three of the 4 isolates were examined in an in vivo experiment, in which mice were challenged intravenously with 1 of 3 isolates and treated daily with amphotericin B, caspofungin, or saline. For the clonality studies, arbitrarily primed polymerase chain reaction (PCR) was performed with the 4 isolates, 8 isolates obtained from nonrelated patients, and a reference strain.. The murine model indicated that 1 isolate was resistant to amphotericin B, 1 had intermediate susceptibility, and 1 was fully susceptible. Two of the 3 isolates were resistant to caspofungin. Microdilution methods did not reliably differentiate between amphotericin B-susceptible and -resistant isolates. All assays identified caspofungin-susceptible and -resistant isolates. Arbitrarily primed PCR showed that the 4 isolates probably were of clonal origin.. We have documented the emergence of amphotericin B-resistant and caspofungin-resistant C. glabrata isolates during treatment of a critically ill liver transplant recipient. Only the Etest predicted amphotericin B resistance in the isolates. We recommend that important fungal strains recovered from patients who are receiving antifungal therapy should be tested for susceptibility to the antifungal drug used, because resistance can be present initially or may occur during treatment.

Topics: Aged; Amphotericin B; Animals; Antifungal Agents; Candida glabrata; Candidiasis; Caspofungin; Critical Illness; Echinocandins; Female; Humans; Lipopeptides; Mice; Microbial Sensitivity Tests; Peptides, Cyclic; Polymerase Chain Reaction

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Critical Illness; Fluconazole; Humans; Male; Middle Aged

Pharmacokinetics of amphotericin B lipid complex (ABLC) was determined in two critically ill patients requiring continuous veno-venous haemofiltration (CVVH) because of acute renal failure. ABLC was administered at a mean daily dose of 4.94 mg/kg for suspected invasive mycosis. Mean C(max) was 0.56 microg/ml, the mean AUC(0-24 h) was 7.46 mgh/l, V(ss) 9.13 l/kg, and t(1/2) was 13.21 h. The haemofilter clearance accounted about 20% of the total ABLC clearance. In one patient sampling was repeated after CVVH had been discontinued. The concentration-time profiles were very similar on and off haemofiltration. Data on our two patients suggest, that pharmacokinetics of ABLC is not significantly affected by CVVH and that ABLC can be administered at the standard doses during CVVH.

Topics: Acute Kidney Injury; Aged; Amphotericin B; Critical Illness; Drug Combinations; Hemodiafiltration; Hemofiltration; Humans; Male; Middle Aged

The clinical features and outcome of the treatment of aspergillosis of the central nervous system (CNS) in Thai patients are presented. The patients who were diagnosed as having CNS aspergillosis by tissue biopsy or culture from January 1, 1991 to December 31, 2000 were retrospectively reviewed. The study variables including age, sex, underlying disease, symptoms and signs, neuro-imaging studies, pathological findings and outcome of treatment, are described. There were seven cases of aspergillosis of the central nervous system. Four patients were male. The median age was 65 years (range 36-78 years). The most common underlying disease was diabetes mellitus (4/7; 57.1%). Two patients (28.6%) had no underlying disease. The most common primary site of infection was the paranasal sinuses (6/7; 85.7%). The most common clinical presentation was headache (6/7; 85.7%). Common neurological signs included multiple cranial nerve palsies (5/7; 71.4%) and alteration of consciousness (3/7; 42.9%). The median duration of the symptoms prior to admission was 60 days (range 8-180 days). All patients were treated with intravenous antifungal agents at high doses. Extensive surgery was performed in 6 patients. The mortality rate was very high (6/7; 85.7%). The median time from diagnosis and treatment to death was 53 days (22-720 days). Aspergillosis of the CNS should be considered in those with clinical features of headache, multiple cranial nerve palsies and alteration of consciousness accompanied by sinusitis, especially in elderly and diabetic patients. It remains a catastrophic opportunistic infection in spite of the current intensive and aggressive treatment.

Topics: Adult; Age Distribution; Aged; Amphotericin B; Antifungal Agents; Aspergillus; Cause of Death; Central Nervous System Fungal Infections; Critical Illness; Female; Humans; Immunocompromised Host; Incidence; Male; Middle Aged; Neuroaspergillosis; Opportunistic Infections; Retrospective Studies; Risk Assessment; Sex Distribution; Survival Analysis; Thailand

The pharmacokinetics of lipid-formulated amphotericin B (AMB), and of AMB that has dissociated from its lipid moiety and bound to lipoproteins in plasma, were separately determined in critically ill patients.. Eleven patients required continuous veno-venous haemofiltration (CVVH). Five of them were treated with liposomal AMB (AmBisome) and seven with AMB colloidal dispersion (Amphocil). Six of the critically ill were not undergoing CVVH (three of them treated with liposomal AMB and three with AMB colloidal dispersion).. Significant amounts of AMB are liberated from liposomes or colloidal dispersion during circulation in plasma, where pharmacokinetics mimic that of AMB deoxycholate. Elimination of the remaining lipid-formulated fraction is different and differentially affected by CVVH. Plasma levels of lipid-formulated AMB were significantly higher in patients treated with liposomal AMB than in those treated with AMB colloidal dispersion; clearance of liposomal AMB is enhanced by haemofiltration, whereas elimination of AMB colloidal dispersion is not significantly affected.. The pharmacokinetics of AMB that has been liberated from its lipid moiety is similar under treatment with either liposomal AMB or AMB colloidal dispersion. Since no significant influence of haemofiltration on the pharmacokinetics of liberated AMB has been found, a standard dose of lipid-formulated AMB can be recommended for patients on haemofiltration.

Topics: Adolescent; Adult; Aged; Amphotericin B; Area Under Curve; Critical Illness; Drug Combinations; Female; Hemofiltration; Humans; Male; Middle Aged; Phosphatidylcholines; Phosphatidylglycerols

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Critical Illness; Fluconazole; Humans; Surgical Procedures, Operative

Topics: Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Candidiasis; Critical Illness; Female; Humans; Inpatients; Male; Middle Aged; Parenteral Nutrition; Retrospective Studies