amphotericin-b and Respiratory-Tract-Infections

Inhaled antibiotics have been used to treat chronic airway infections since the 1940s. The earliest experience with inhaled antibiotics involved aerosolizing antibiotics designed for parenteral administration. These formulations caused significant bronchial irritation due to added preservatives and nonphysiologic chemical composition. A major therapeutic advance took place in 1997, when tobramycin designed for inhalation was approved by the U.S. Food and Drug Administration (FDA) for use in patients with cystic fibrosis (CF) with chronic Pseudomonas aeruginosa infection. Attracted by the clinical benefits observed in CF and the availability of dry powder antibiotic formulations, there has been a growing interest in the use of inhaled antibiotics in other lower respiratory tract infections, such as non-CF bronchiectasis, ventilator-associated pneumonia, chronic obstructive pulmonary disease, mycobacterial disease, and in the post-lung transplant setting over the past decade. Antibiotics currently marketed for inhalation include nebulized and dry powder forms of tobramycin and colistin and nebulized aztreonam. Although both the U.S. Food and Drug Administration and European Medicines Agency have approved their use in CF, they have not been approved in other disease areas due to lack of supportive clinical trial evidence. Injectable formulations of gentamicin, tobramycin, amikacin, ceftazidime, and amphotericin are currently nebulized "off-label" to manage non-CF bronchiectasis, drug-resistant nontuberculous mycobacterial infections, ventilator-associated pneumonia, and post-transplant airway infections. Future inhaled antibiotic trials must focus on disease areas outside of CF with sample sizes large enough to evaluate clinically important endpoints such as exacerbations. Extrapolating from CF, the impact of eradicating organisms such as P. aeruginosa in non-CF bronchiectasis should also be evaluated.

Topics: Administration, Inhalation; Amikacin; Amphotericin B; Anti-Bacterial Agents; Aztreonam; Ceftazidime; Colistin; Cystic Fibrosis; Gentamicins; Humans; Nebulizers and Vaporizers; Respiratory Tract Infections; Tobramycin

Fungi, in comparison with other pathogenic factors, have high pathogenicity. The number of fungal species which are able to infect people is over 500. The upper respiratory tract and ear have permanent contact with external environment which makes their ontocenoses open to continuous exchange of microorganisms of which they consist. In etiology of inflammatory processes 21 species which belonging to 3 genera (Zygomycota, Ascomycota, Basidiomycota) of fungi play important role. Administration of antifungal drugs can be: prophylactic, empiric preemptive and therapeutic. Physicians may prescribe antibiotics (mainly pollens: amphotericin B, natamycin and nystatin) and chemiotherapeutics (mainly azoles and fluorpirymidins, pigments, chlorhexidine and chlorquinaldol). In ENT practice topical and systemic drugs can be administrated. Topical lozenges include amphotericin B, clotrimazole, chlorhexidine or chlorquinaldol and oral gels: nystatin and miconazole. Some of drugs are in the form of suspension/solution, which can be used for inhalation, into the sinus, for swabbing or for lavage: amphotericin B, natamycin, nystatin, clotrimazol, flucytosine, miconazole, fluconazole, vorykonazole, caspofungin. It should be underlined that only a few of dugs can be absorbed from the digestive tract: flucytosine, fluconazole, itraconazole, ketoconazole, miconazole, vorykonazole.

Topics: Administration, Inhalation; Administration, Oral; Administration, Topical; Amphotericin B; Antifungal Agents; Azoles; Clotrimazole; Ear Diseases; Humans; Miconazole; Mycoses; Nystatin; Otitis; Respiratory Tract Infections

During the last decade the incidence of invasive aspergillosis has substantially grown due to the increasing use of powerful immunosupressive drugs in more patients. Unfortunately, the associated mortality with this infection is still very high and has not decreased in recent years. Pulmonary aspergillosis is by far the most frequent clinical picture of this infection, followed by sinus, tracheo-bronchial and central nervous system disease. The degree of immunosupression is the main factor influencing the evolution and dissemination of aspergillosis. Conventional amphotericin B has been the first-line therapy of invasive aspergillosis for the last 30 years, and most authors have long considered amphotericin B related toxicity as one of the main causes for the poor results obtained in the outcome of patients who developed this infection. Fortunately, in the last few years new safer and more effective drugs have been developed for the treatment of this entity. However, if we are really trying to substantially decrease invasive aspergillosis associated-mortality we should use these drugs earlier in the development of the infection, using new more sensitive diagnostic tests and/or a riskbase strategy which could identify patients at the highest risk to develop this infection.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillosis, Allergic Bronchopulmonary; Caspofungin; Dermatomycoses; Drug Therapy, Combination; Echinocandins; Humans; Immunocompromised Host; Immunologic Factors; Itraconazole; Lipopeptides; Neuroaspergillosis; Neutropenia; Peptides; Peptides, Cyclic; Pyrimidines; Respiratory Tract Infections; Triazoles; Voriconazole

Topics: Administration, Inhalation; Aerosols; Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Antiprotozoal Agents; Chronic Disease; Cystic Fibrosis; Drug Resistance, Microbial; Forecasting; Humans; Immunocompromised Host; Respiratory Tract Infections

Topics: Aminoglycosides; Amphotericin B; Anti-Infective Agents; Cephalosporins; Cephamycins; Chloramphenicol; Clindamycin; Erythromycin; Flucytosine; Humans; Miconazole; Penicillins; Respiratory Tract Infections; Tetracycline; Vancomycin

The literature on the clinical use of rifampicin in combination for the treatment of non-mycobacterial diseases is reviewed. From the published evidence, the most promising associations are, for staphylococcal infections, gentamicin, erythromycin, kanamycin and fusidic acid. In the field of Gram-negative infections, Psuedomonas-induced sepsis in particular, data are not so impressive but promising results have been obtained with the associated use of rifampicin and gentamicin or colistin. Some systemic fungal diseases may be successfully treated with rifampicin in combination with amphotericin-B. Although only few reports are available on this subject, the importance of such an application is stressed in view of the severity of these diseases and of the lack of appropriate treatments.

Topics: Amphotericin B; Cephalosporins; Chloramphenicol; Colistin; Drug Therapy, Combination; Endocarditis, Bacterial; Erythromycin; Gentamicins; Humans; Kanamycin; Lincomycin; Mycoses; Nalidixic Acid; Penicillins; Pseudomonas Infections; Respiratory Tract Infections; Rifampin; Staphylococcal Infections; Sulfamethoxazole; Tetracyclines; Trimethoprim; Urinary Tract Infections; Vancomycin

The influence of topical antimicrobial prophylaxis (TAP) on colonization of oropharynx and trachea was studied in patients receiving and not receiving prophylaxis. Twenty-two patients in Intensive Care Unit (ICU) I (Group 1) received TAP (tobramycin, colistin, and amphotericine B in oropharynx and stomach). Simultaneous to Group 1, 21 patients (Group 2) not receiving TAP were studied in ICU I. A control group of patients admitted to another, identical, ICU (ICU II), where no TAP was administered, were studied simultaneously (Group 3a, n = 23). A second control group (Group 3b, n = 31), was formed by collecting data from patients admitted to ICU I in Period II. Patients receiving TAP were less frequently colonized than patients not receiving prophylaxis. Moreover, of the patients not receiving TAP, those staying in the ICU where TAP was administered (Group 2) were less frequently colonized than patients in another ICU (Group 3). Of the patients not colonized on admission, those staying in the ICU where TAP was administered remained free of colonization for a longer time. In the ICU where no TAP was administered, more patients were colonized simultaneously and cross-acquisition occurred more frequently. TAP significantly influenced colonization of oropharynx and trachea in patients receiving and not receiving prophylaxis within the same ICU as compared with patients not receiving prophylaxis in another identical ICU.

Topics: Administration, Topical; Aged; Amphotericin B; Colistin; Colony Count, Microbial; Cross Infection; Drug Therapy, Combination; Enterobacteriaceae; Female; Humans; Intensive Care Units; Male; Middle Aged; Oropharynx; Prospective Studies; Pseudomonadaceae; Respiratory Tract Infections; Tobramycin; Trachea

The objective of this study was to assess the effect of a novel regimen of antibiotic prophylaxis on the incidence of lower respiratory tract infection in patients requiring prolonged (at least five days) mechanical ventilation. The design was a controlled, prospective, randomized trial, with blinded comparison of the groups regarding the incidence of respiratory tract infection in an intensive care unit of a university hospital. After determination of the APACHE II score for severity of disease, 88 patients were randomly divided in three groups. Twenty-four of these patients did not complete five days of mechanical ventilation, and eight were withdrawn for other reasons. Fifty-six patients (18 in group 1, 21 in group 2, 17 in group 3) completed the study. Patients in both control groups 1 and 2 did not receive antibiotic prophylaxis, but the two groups differed in the antibiotic policy in case of infection. Patients in group 3 received antibiotic prophylaxis consisting of norfloxacin, polymyxin E, and amphotericin B, applied topically in oropharynx and stomach from time of ICU admission until extubation, and intravenous cefotaxime 500 mg three times a day during the first five days of admission. In both control groups, about 90 percent of the patients acquired microbial colonization of oropharynx or stomach. In group 3, only 12 percent and 24 percent of the patients acquired colonization of oropharynx and stomach, respectively (p less than 0.001). This resulted in a reduction of the incidence of lower respiratory tract infection (78 percent in group 1, 62 percent in group 2, 6 percent in group 3 [p = 0.0001]). The regimen of antibiotic prophylaxis studied prevented respiratory tract infection in mechanically ventilated patients. Antibiotic prophylaxis should be considered in all patients expected to require prolonged mechanical ventilation.

Topics: Administration, Topical; Amphotericin B; Bacteria; Cefotaxime; Colistin; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Infusions, Intravenous; Intensive Care Units; Male; Middle Aged; Norfloxacin; Oropharynx; Prospective Studies; Respiration, Artificial; Respiratory Tract Infections; Severity of Illness Index; Stomach

A comparative, prospective study was made of the incidence of infection in the lower airway (purulent tracheobronchitis and pneumonia) in long-term patients who were mechanically ventilated due to respiratory failure of noninfectious origin. Twenty-eight patients were randomly allocated into a study group (A, n = 13) in which a nonabsorbable paste containing 2% tobramycin, 2% amphotericin B, and 2% polymyxin E was administered locally to decontaminate the oropharynx, and a control group (B, n = 15) in which a paste without antibiotics was also applied to the oropharynx. We studied the effectiveness of the prophylactic technique in decontaminating the oropharynx and trachea of organisms potentially pathogenic for the respiratory system. Decontamination was successful in ten of 13 patients in group A vs. one of 15 patients in group B (p less than .001). The results demonstrated a lower rate of infection in the lower respiratory tract in the study group (three patients with tracheobronchitis and no pneumonias) than in the control group (three patients with tracheobronchitis and 11 with pneumonia), the difference between both being highly significant (p less than .001). Two (15%) patients in group B developed sepsis of pulmonary origin. None of the patients on prophylactic treatment developed this complication. Although the overall mortality was similar in both groups (group A, 30% vs. group B, 33%), we believe that infection contributed to a great extent to the death of two of five patients in group B. We conclude that nosocomial pneumonia, which is a frequent complication in critically ill patients on mechanical ventilation, could be prevented by local application of nonabsorbable antibiotics to the oropharynx.

Topics: Administration, Topical; Adolescent; Adult; Aged; Amphotericin B; Child; Colistin; Cross Infection; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Oropharynx; Prospective Studies; Respiration, Artificial; Respiratory Tract Infections; Tobramycin

In a randomized clinical trial the prophylactic effects of locally administered antimicrobials on quantitative colonization and respiratory infections were studied in intubated patients with an expected period of mechanical ventilation of greater than 6 days. Nineteen patients received 50 mg of polymyxin B and 80 mg of gentamicin distributed among nose, oropharynx and stomach at 6-h intervals, as well as 300 mg of amphotericin B in the oropharynx. Twenty untreated patients served as controls. In the control group colonization by respiratory pathogens was more common (oropharynx 19 vs 6 patients (p less than 0.001); trachea 19 vs 11 (p less than 0.01)), and the number as well as the count of the colonizing species was usually higher. Fourteen patients of the control group developed respiratory infections, including nine cases of pneumonia, as compared to four patients with prophylaxis, including one case of pneumonia (p less than 0.01). Pneumonia-associated deaths were prevented with prophylaxis; however, the overall mortality remained unchanged. Respiratory infections in the prophylaxis group were associated with organisms resistant to the agents used, but the overall occurrence of resistance was not increased, as compared to the control group. We conclude that unrestrained upper airway colonization by respiratory pathogens and respiratory tract infection were causally related. Local antimicrobial prophylaxis proved to be a highly effective strategy for the prevention of potentially life-threatening pneumonias in critically ill patients, but in the present study the host setting appeared to be the major determinant of outcome.

Topics: Administration, Intranasal; Administration, Topical; Amphotericin B; Clinical Trials as Topic; Female; Gentamicins; Humans; Male; Middle Aged; Oropharynx; Polymyxin B; Polymyxins; Random Allocation; Respiration, Artificial; Respiratory Tract Infections; Stomach; Time Factors

Pulmonary cryptococcosis develops not only in immunocompromised patients but also in immunocompetent patients. However, lymph node involvement is relatively rare in immunocompetent patients. We herein report the case of an 80-year-old man who was not in an apparent immunocompromised state but was diagnosed with pulmonary cryptococcosis with mediastinal lymphadenopathy. The patient was resistant to fluconazole and voriconazole monotherapy; thus, his lung lesions significantly worsened. He eventually responded well to a combination therapy of amphotericin B and flucytosine, which was administered according to the treatment strategy for disseminated diseases.

Topics: Aged, 80 and over; Amphotericin B; Antifungal Agents; Cryptococcosis; Drug Therapy, Combination; Drug Tolerance; Flucytosine; Humans; Lymphadenopathy; Male; Respiratory Tract Infections

Pulmonary coinfection with Mucor and Aspergillus species has not been reported in organ transplant recipients. Here, we report a rare case of pulmonary coinfection with invasive fungal species in a renal transplant recipient with delayed graft function. The patient was first treated with a regime containing voriconazole, but the infection only worsened. Then, bronchoalveolar lavage fluid culture and internal transcribed spacer region sequencing were performed, and simultaneous pulmonary infection by Lichtheimia ramosa and Aspergillus fumigatus was clearly diagnosed. Susceptibility testing determined that the fungi were sensitive to amphotericin B and posaconazole. Therefore, a therapeutic regime containing posaconazole and amphotericin B liposome, which are less toxic to the kidney, was planned and resulted in resolution of the infectious symptoms. The present case demonstrates the importance of identifying fungal pathogens early and definitively, determining the effective anti-fungal medications, and administering the properly planned therapeutic regime in a timely manner to treat cases of coinfection in transplant recipients.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Coinfection; Delayed Graft Function; Humans; Immunocompromised Host; Kidney Transplantation; Male; Mucorales; Mucormycosis; Respiratory Tract Infections; Triazoles

To determine the prevalence and antifungal susceptibility pattern of Candida species.. This prospective, cross-sectional study was conducted at the Quaid-e-Azam International Hospital, Islamabad, Pakistan, from January 2014 to February 2015, and comprised different clinical samples which were analysed for various types of microbial infections. Species differentiation was confirmed by biochemical and molecular methods. Antifungal susceptibility against amphotericin B, fluconazole and voriconazole was determined by Clinical and Laboratory Standards Institute M44-A disk diffusion method.. Of the 219 Candida isolates, majority of them were isolated from urine 78(35.6%) and vaginal swabs 59(26.9%). Moreover, 144(65.8%) samples were of females and 75(34.2%) were of males. Candida albicans 128(58.45%) was the most predominant species followed by Candida glabrata 30(13.69%), Candida tropicalis 26(11.87%), Candida krusei 17(7.76%), Candida parapsilosis 12(5.47%), Candida dubliniensis 3(1.37%) and Candida lusitaniae 3(1.37). All isolates were least susceptible to amphotericin B with a susceptibility rate of 213(97.26%). The highest resistance was found for voriconazole 40(18.26%) compared to fluconazole 32(14.61%).. Candida species possessed high resistance rate against various antifungal agents.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Candida; Candida albicans; Candida glabrata; Candida parapsilosis; Candida tropicalis; Candidiasis; Candidiasis, Vulvovaginal; Child; Child, Preschool; Cross-Sectional Studies; Drug Resistance, Fungal; Female; Fluconazole; Humans; Infant; Infant, Newborn; Inpatients; Male; Microbial Sensitivity Tests; Middle Aged; Molecular Epidemiology; Outpatients; Pakistan; Prevalence; Prospective Studies; Respiratory Tract Infections; Tertiary Care Centers; Urinary Tract Infections; Voriconazole; Young Adult

Our aim was to assess the impact of positive cultures for non-Aspergillus molds on the risk of progression to invasive fungal infection (IFI), and the effect of prophylactic nebulized liposomal amphotericin B (n-LAB) on these pathogens.. This was an observational study (2003-2013) including lung transplant recipients (LTR) receiving lifetime n-LAB prophylaxis, in whom non-Aspergillus molds were isolated on respiratory culture before and after transplantation (minimum 1-year follow-up).. We studied 412 patients, with a mean postoperative follow-up of 2.56 years (interquartile range 1.01-4.65). Pre- and post-transplantation respiratory samples were frequently positive for non-Aspergillus molds (11.9% and 16.9% of LTR respectively). Post transplantation, 10 (2.42%) patients developed non-Aspergillus mold infection (4 Scedosporium species, 4 Purpureocillium species, 1 Penicillium species, and 1 Scopulariopsis species); 5 (1.21%) had IFI, with 60% IFI-related mortality. Non-Aspergillus molds with intrinsic amphotericin B (AB) resistance were more commonly isolated in bronchoscopy samples than AB-variably sensitive or AB-sensitive molds (54.5% vs. 25%, P = 0.04) and were associated with a higher risk of infection (56.3% vs. 1.3%%, P < 0.01).. In LTR undergoing n-LAB prophylaxis, pre- and post-transplantation isolation of non-Aspergillus molds is frequent, but IFI incidence (1.21%) is low. Purpureocillium is an emerging mold. AB-resistant non-Aspergillus species were found more often in bronchoscopy samples and were associated with a higher risk of infection.

Topics: Adult; Amphotericin B; Antifungal Agents; Ascomycota; Female; Fungi; Humans; Invasive Fungal Infections; Lung Transplantation; Male; Middle Aged; Penicillium; Respiratory Tract Infections; Scedosporium; Scopulariopsis; Transplant Recipients; Young Adult

Invasive fungal infections are a major cause of morbidity and mortality among solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients, but few data have been reported on the epidemiology of endemic fungal infections in these populations.. Fifteen institutions belonging to the Transplant-Associated Infection Surveillance Network prospectively enrolled SOT and HCT recipients with histoplasmosis, blastomycosis, or coccidioidomycosis occurring between March 2001 and March 2006.. A total of 70 patients (64 SOT recipients and 6 HCT recipients) had infection with an endemic mycosis, including 52 with histoplasmosis, 9 with blastomycosis, and 9 with coccidioidomycosis. The 12-month cumulative incidence rate among SOT recipients for histoplasmosis was 0.102%. Occurrence of infection was bimodal; 28 (40%) infections occurred in the first 6 months post transplantation, and 24 (34%) occurred between 2 and 11 years post transplantation. Three patients were documented to have acquired infection from the donor organ. Seven SOT recipients with histoplasmosis and 3 with coccidioidomycosis died (16%); no HCT recipient died.. This 5-year multicenter prospective surveillance study found that endemic mycoses occur uncommonly in SOT and HCT recipients, and that the period at risk extends for years after transplantation.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Blastomycosis; Child; Coccidioidomycosis; Coinfection; Comorbidity; Endemic Diseases; Female; Hematopoietic Stem Cell Transplantation; Histoplasmosis; Humans; Incidence; Itraconazole; Male; Middle Aged; Organ Transplantation; Prospective Studies; Respiratory Tract Infections; Time Factors; United States; Young Adult

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

To describe a case of successful treatment of severe pulmonary blastomycosis with amphotericin B deoxycholate after failure of liposomal amphotericin B.. A 35-year-old male was exposed to damp decomposing wood while cleaning his basement. He subsequently developed a cough, malaise, fever, nausea, vomiting, and diarrhea. He was admitted to the hospital and intubated for worsening pulmonary symptoms. Microscopic examination of his sputum indicated Blastomyces dermatitidis. Liposomal amphotericin B was administered for 6 days, but the patient's temperature reached 39.6 °C and his white blood cell (WBC) count reached 52,300/μL. Extensive consolidation of both lungs fields was observed on chest X-ray. Because of progressive clinical deterioration, the treatment was switched to amphotericin B deoxycholate by continuous infusion. That change resulted in clinical improvement, with abrupt reductions (within 48 hours) in temperature and the WBC count. By day 14 of therapy (day 8 of amphotericin B deoxycholate), the chest X-ray showed improvement in diffuse airspace filling. After 16 days of amphotericin B treatment, intravenous followed by oral voriconazole was administered for 3 months. Eight months later the patient's strength had improved significantly, but he still had occasional episodes of shortness of breath.. The management of blastomycosis is challenging because of the lack of clinically supporting data. The gold standard for severe pulmonary blastomycosis had been amphotericin B deoxycholate; however, improved safety data with liposomal amphotericin B for other fungal infections has suggested this as an effective alternative. This report describes a patient with severe pulmonary blastomycosis failing 6 days of liposomal amphotericin B, yet he tolerated and clinically responded to continuous infusion of amphotericin B deoxycholate. Based on this case report and a simulated pharmacokinetic/pharmaco dynamic analysis, continuous infusion of amphotericin B deoxycholate may be a reasonable option for enhanced efficacy and minimal toxicity in patients with blastomycosis.. Ours is the first case report to use continuous infusion of amphotericin B deoxycholate for the management of pulmonary blastomycosis. These results suggest that liposomal amphotericin B may not be adequate in some patients for the management of B. dermatitidis pulmonary infections.

Topics: Adult; Amphotericin B; Antifungal Agents; Blastomycosis; Humans; Infusions, Intravenous; Male; Respiratory Tract Infections; Treatment Failure; Treatment Outcome

Invasive fungal infections (IFIs) still pose major challenges in allogeneic hematopoietic SCT (HSCT), and effective antifungal prophylaxis remains a matter of debate. The aim of this retrospective study was to evaluate the toxicity and the impact of aerosolized deoxycholate amphotericin B (aero-d-AmB) on respiratory tract IFIs (airways IFIs) in a homogeneous cohort of allogeneic HSCT patients, transplanted at one institution. Since 1999, 102 consecutive patients were transplanted from matched related (N = 71) or unrelated donor (MUD). Aero-d-AmB was administered for a median time of 16 days (range 2-45), in addition to systemic antifungal prophylaxis. Prolonged administration was neither associated with increased severe bacterial infections, nor with severe adverse events. In 16 patients in whom aero-d-AmB was delivered for less than 8 days, due to worsened clinical conditions or poor compliance, proven or probable airways IFIs were diagnosed in three cases (one mucormycosis and one fusariosis and one probable aspergillosis), whereas in 84 patients receiving aero-d-AmB for ≥ 8 days, one possible and one probable aspergillosis were diagnosed. A shortened administration (< 8 days) of aero-d-AmB was therefore associated with an increased risk of both total airways IFIs (P = 0.027) and proven/probable IFIs (P = 0.012). At multivariate analysis prolonged aero-d-AmB administration retained an independent protective effect on airways IFIs (P = 0.026) whereas a MUD transplant was associated with a borderline increase of IFIs risk (P=0.052). Overall, 95.1% of patients did not experience airways IFIs and no patient died due to IFIs. In this cohort of patients, prolonged aero-d-AmB seems to have a role in preventing respiratory tract IFIs, but a randomized controlled trial is recommended to verify the impact of this prophylaxis in the setting of allogeneic HSCT.

Topics: Adolescent; Adult; Aerosols; Aged; Amphotericin B; Antifungal Agents; Cohort Studies; Deoxycholic Acid; Drug Combinations; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppression Therapy; Incidence; Italy; Lymphoproliferative Disorders; Male; Middle Aged; Mycoses; Respiratory System; Respiratory Tract Infections; Retrospective Studies; Risk Factors; Transplantation, Homologous; Young Adult

A three-month laboratory-based prospective survey was conducted at four major university hospitals covering one-third of the Danish population in order to determine the prevalence, significance, and susceptibility pattern of aspergilli in airway samples. Samples received in January-March 2007 for routine microbiologic investigation were examined for Aspergillus following routine procedures and with extended incubation (5 days). Identification was done by morphologic criteria and susceptibility testing using EUCAST method for azoles and amphotericin B E-test. Invasive aspergillosis (IA) was evaluated using modified EORTC/MSG criteria. A total of 11,368 airway samples were received. Growth of Aspergillus spp. was found in 129 and 151 patients using routine and extended incubation, respectively. Three patients had proven IA (2%), 11 probable (7%), four had allergic bronchopulmonary aspergillosis (ABPA) (3%), but the majority was colonised (88%). Underlying conditions were cystic fibrosis in 82 patients (55%), chronic obstructive pulmonary disease in 19 (13%) and haematological disorder in 11 (7%). Twenty-six patients (18%) were at intensive care unit and 69 (47%) received steroid treatment. Azole MICs were elevated for five isolates as follows (itraconazole, posaconazole, voriconazole MICs [mg/L]): two A. fumigatus isolates (>4; >4; 2 and >4; 0.125; 1), one A. lentulus isolate (2; 2; 0.5) and two A. terreus isolates (2; 2; 2 and 2; 0.125; 1). For four isolates the amphotericin B MIC was >1 μg/ml (3/112 A. fumigatus, 1/2 A. terreus). In conclusion, Aspergillus appears to be an important pathogen in Denmark. Elevated itraconazole MICs were detected in 4% of the isolates including a multi-azole resistant isolate.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Child; Child, Preschool; Denmark; Drug Resistance, Fungal; Female; Hospitals; Humans; Itraconazole; Male; Microbial Sensitivity Tests; Middle Aged; Prevalence; Prospective Studies; Pyrimidines; Respiratory System; Respiratory Tract Infections; Treatment Outcome; Triazoles; Voriconazole

Aspergillus fumigatus is a leading cause of death in immunocompromised patients and a frequent colonizer of the respiratory tracts of asthma and cystic fibrosis (CF) patients. Biofilms enable bacteria and yeasts to persist in infections and can contribute to antimicrobial resistance. We investigated the ability of A. fumigatus to form biofilms on polystyrene (PS) and human bronchial epithelial (HBE) and CF bronchial epithelial (CFBE) cells. We developed a novel in vitro coculture model of A. fumigatus biofilm formation on HBE and CFBE cells. Biofilm formation was documented by dry weight, scanning electron microscopy (SEM), and confocal scanning laser microscopy (CSLM). The in vitro antifungal activities of seven antifungal drugs were tested by comparing planktonic and sessile A. fumigatus strains. A. fumigatus formed an extracellular matrix on PS and HBE and CFBE cells as evidenced by increased dry weight, SEM, and CSLM. These biofilms exhibited decreased antifungal drug susceptibility and were adherent to the epithelial cells, with fungi remaining viable throughout 3 days. These observations might have implications for treatment of A. fumigatus colonization in chronic lung diseases and for its potential impact on airway inflammation, damage, and infection.

Topics: Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Biofilms; Bronchi; Cells, Cultured; Cystic Fibrosis; Drug Resistance, Fungal; Epithelial Cells; Humans; Microbial Sensitivity Tests; Microscopy, Confocal; Microscopy, Electron, Scanning; Respiratory Tract Infections

We report a pulmonary mucormycosis due to Absidia corymbifera. It occurred in a leukemic patient treated for a probable aspergillosis regressing after voriconazole treatment. The patient responded to surgery and a combination of liposomal amphotericin B and itraconazole. He was alive and well after 7-months of follow up.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Drug Therapy, Combination; Humans; Itraconazole; Leukemia; Male; Radiography, Thoracic; Respiratory Tract Infections; Treatment Outcome; Zygomycosis

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Critical Care; Female; Fluconazole; Flucytosine; Fungi; Humans; Itraconazole; Lung Diseases, Fungal; Male; Microbial Sensitivity Tests; Middle Aged; Respiratory Tract Infections; Spain; Trichosporon

Invasive aspergillosis is the leading cause of early death in many transplant centers and has a major impact on the management of hematologic malignancies. The mortality rate with current therapy (amphotericin B and surgery) has remained unacceptably high. In vitro data along with a few case reports have suggested a potential benefit of hyperbaric oxygen (HBO).. We retrospectively studied all patients referred to our service when histologic specimens suggested invasive aspergillosis. Our main assessment of outcome was survival 3 months after initiation of HBO.. Ten patients were included. All received adjunctive HBO along with the standard of care. Rhinosinusinal infection was the primary presentation. The most common underlying conditions were hematologic malignancies. Six patients were free of signs of infection 3 months after the first HBO treatment.. Adjunctive HBO appears to be a valuable tool in this devastating condition. Further studies are warranted to clarify its role.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Child; Child, Preschool; Combined Modality Therapy; Female; Humans; Hyperbaric Oxygenation; Male; Middle Aged; Respiratory Tract Infections; Retrospective Studies; Survival Rate; Tomography, X-Ray Computed; Treatment Outcome

Localised fungal infection of the larynx and tracheobronchial tree is extremely uncommon. We report the case of a 6-year-old girl with acute lymphocytic leukaemia, who developed symptoms of upper airways obstruction 6 months after a cord blood transplant. Bronchoscopy showed a pale plaque lesion in the larynx and tracheobronchial tree. Aspergillus fumigatus was cultured from a biopsy of the lesion. The patient was treated successfully with a prolonged course of amphotericin B and assessed with multiple surveillance bronchoscopies.

Topics: Amphotericin B; Anti-Bacterial Agents; Aspergillosis; Aspergillus fumigatus; Biopsy; Bone Marrow Transplantation; Bronchitis; Child; Female; Humans; Laryngitis; Larynx; Postoperative Complications; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Respiratory Tract Infections; Tracheitis

Topics: Amphotericin B; Antifungal Agents; Biopsy; Diagnosis, Differential; Fusarium; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lung; Male; Middle Aged; Mycoses; Penile Diseases; Respiratory Tract Infections; Spain; Tomography, X-Ray Computed; Ulcer

The use of indwelling central catheters for long-term administration of hyperalimentation, chemotherapy or other intravenous therapies is increasing. This unusual presentation of a catheter-induced right atrial thrombus was complicated by fungal infection. We present a case of a paediatric sickle-cell patient who underwent surgical removal of a right atrial thrombus secondary to fungal (Candida tropicalis) endocarditis from an indwelling catheter. Successful thrombus removal utilizing cardiopulmonary bypass and subsequent discharge underscores the importance of surgical therapy in treating this important complication.

Topics: Amphotericin B; Anemia, Sickle Cell; Antifungal Agents; Blood Transfusion; Candidiasis; Cardiopulmonary Bypass; Catheterization, Central Venous; Child, Preschool; Combined Modality Therapy; Embolism; Endocarditis; Heart Atria; Heart Diseases; Humans; Intraoperative Complications; Male; Postoperative Complications; Respiratory Tract Infections; Thrombosis

The aim of the study was the estimation of in vitro susceptibility to antifungal agents of yeast isolated from sputum of 70 respiratory diseases patients using the disc-diffusion method-antimycogram. The following agents were tested: amphotericin B, 5-fluorocytosine, nystatin, ketoconazole, fluconazole. Only Candida strains were isolated from sputum, 82% of them were Candida albicans. We noted differences in susceptibility to antimycotics of Candida strains. The best antimycotic in vitro was 5-fluorocytosine. 54% of isolated Candida strains were resistant to 1 or more antimycotics.

Topics: Adult; Aged; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Candida; Candidiasis; Fluconazole; Flucytosine; Humans; Ketoconazole; Microbial Sensitivity Tests; Middle Aged; Nystatin; Respiratory Tract Infections; Species Specificity; Sputum

122 Aspergillus strains were isolated from respiratory specimens from 80 patients. Aspergillus fumigatus was the most common species, constituting 88% of the isolates. Susceptibility testing by the NCCLS broth macrodilution procedure revealed that the minimal inhibitory concentration for 50% of the strains (MIC50) was 0.25 mg/l for itraconazole and 0.5 mg/l for amphotericin B. The MIC90 was 1 mg/l for both drugs. To our knowledge, no cases of in vitro resistance during long-term itraconazole use in treatment of Aspergillus infection have been documented. We identified 3 patients infected with A. fumigatus strains that acquired in vitro resistance to itraconazole during prolonged therapy. This finding supports the importance of susceptibility testing.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Drug Resistance, Microbial; Humans; Itraconazole; Microbial Sensitivity Tests; Respiratory Tract Infections

Invasive aspergillosis is a serious opportunistic infection in immunocompromised patients. The case history is described of a 44 year old patient with peripheral T cell lymphoma who developed hoarseness and stridor after chemotherapy. Aspergillus fumigatus was isolated repeatedly from the sputum. Bronchoscopic examination showed symmetrical creamy-white exophytic lesions involving both vocal cords and the supraglottic area. There was diffuse tracheobronchitis with multiple raised cream-coloured plaques in the trachea which histologically consisted of numerous septate branching hyphae consistent with Aspergillus species. The lesions responded to systemic treatment with amphotericin B.

Topics: Adult; Amphotericin B; Aspergillosis; Aspergillus fumigatus; Bronchitis; Humans; Itraconazole; Laryngitis; Lymphoma, T-Cell, Peripheral; Male; Respiratory Sounds; Respiratory Tract Infections; Tracheitis

Spontaneous remission without any anti-cancer therapy in a 57-year-old woman with adult T-cell leukemia (ATL) is reported. The patient was referred to our department because of persistent cough and appearance of abnormal lymphocytes in the peripheral blood, and she was diagnosed as having chronic ATL. Eight months later, she was re-admitted because of cystitis, watery diarrhea and worsening of respiratory symptoms with an increase of ATL cells (WBC 31 x 10(9)/l with 56% ATL cells). Acute exacerbation of ATL was diagnosed. Interestingly, antibiotic therapy for the pulmonary and urinary tract infections brought about spontaneous reduction of the ATL cell count. Spontaneous remission of ATL continued for one year without chemotherapy. The role of infection as a trigger of acute exacerbation and spontaneous remission of ATL is discussed.

Topics: Amphotericin B; Ampicillin; Bone Marrow; Candidiasis; Cystitis; Diarrhea; Escherichia coli Infections; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Leukemia, Prolymphocytic, T-Cell; Middle Aged; Remission, Spontaneous; Respiratory Tract Infections; T-Lymphocytes

In a pilot study, a prophylactic regimen including ciprofloxacin and amphotericin B was applied in 102 consecutive patients on artificial respiration for greater than or equal to 5 days to prevent respiratory tract infection with aerobic Gram-negative bacilli. Ciprofloxacin was given twice a day, as 500 mg through a gastric tube or 200 mg intravenously, and both applications led to negative cultures for aerobic Gram-negative bacilli from faeces and throat, except for a few periods of carriage lasting only a few days. No patient acquired respiratory tract infection with one of the Enterobacteriaceae or Pseudomonadaceae after 4 days of artificial respiration. In contrast to other prophylactic regimens in intensive care patients, this regimen is relatively simple and effective. These preliminary data suggest that this regimen should be studied further with special emphasis on the induction of resistance in Intensive Care Units using prospective, double-blind study designs.

Topics: Amphotericin B; Bronchitis; Ciprofloxacin; Cross Infection; Drug Therapy, Combination; Feces; Female; Gram-Negative Bacteria; Humans; Male; Middle Aged; Pharynx; Pilot Projects; Respiration, Artificial; Respiratory Tract Infections; Sputum

The incidence of respiratory tract infections was determined in 59 multiple trauma patients requiring prolonged intensive care (greater than 5 days) and receiving no antibiotic prophylaxis. Early pneumonia (less than 48 hr) with S. aureus, S. pneumoniae, and/or H. influenzae was found in 44% of patients. Secondary colonization of the oropharynx and respiratory tract with ICU-associated Gram-negative bacilli followed by pneumonia occurred in 12 patients (20%). The overall incidence of respiratory tract infections was 59%. In a prospective open trial three prophylactic antibiotic regimens were compared: 17 patients were treated with intestinal decontamination using nonabsorbable antibiotics (polymyxin E 400 mg, tobramycin 320 mg, amphotericin B 2,000 mg/day). No difference in infection rate was found. Twenty-five patients were treated with intestinal and oropharyngeal decontamination using an ointment containing 2% of the same antibiotics. Secondary colonization and infection of the respiratory tract with Gram-negative bacilli was significantly reduced (p less than 0.001). The incidence of early (Gram-positive) infections, however, was unchanged. Another group of 63 patients was treated with systemic antibiotic prophylaxis during the first days in combination with oropharyngeal and intestinal decontamination. The incidence of early pneumonia was significantly reduced (p less than 0.001). Five patients (8%) developed an infection. Superinfections were not observed.

Topics: Administration, Topical; Adolescent; Adult; Amphotericin B; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Cross Infection; Decontamination; Female; Humans; Intestines; Male; Middle Aged; Oropharynx; Pneumonia; Pneumonia, Staphylococcal; Polymyxins; Prospective Studies; Respiratory System; Respiratory Tract Infections; Retrospective Studies; Tobramycin; Wounds and Injuries

One of the most frequent complications encountered in non-specific respiratory pathology of recent years is overinfection by Candida albicans. An important contributive factor is the recent massive antibiotherapy, above all with tetracyclines, favouring this overinfection. Since at present the treatment of bronchopulmonary processes is difficult owing to the lack of an effective oral or parenteral therapy, a study was carried out of 33 patients treated with nystatin and amphotericin B in aerosol form, with 3-4 sessions of treatment per day, during a minimum of 10 days. At each session either 50,000 U of nystatin or 5 mg of amphotericin B were administered. The results obtained showed that after treatment, C. albicans was no longer present in the sputum of 84% of cases treated. In view of these results it is considered that - at present - the two most suitable substances for the treatment of pulmonary candidiases are nystatin and amphotericin B in aerosol form.

Topics: Adolescent; Adult; Aerosols; Aged; Amphotericin B; Candida albicans; Candidiasis; Female; Humans; Male; Middle Aged; Nystatin; Respiratory Tract Infections; Sputum

Topics: Amebiasis; Amoeba; Amphotericin B; Anti-Bacterial Agents; Cerebrospinal Fluid; Disease Models, Animal; Humans; Meningoencephalitis; Respiratory Tract Infections; Sports Medicine; Staining and Labeling; Swimming; United States

Topics: Adult; Amphotericin B; Antilymphocyte Serum; Azathioprine; Dactinomycin; Female; Heart Transplantation; Humans; Infections; Male; Middle Aged; Mycoses; Nystatin; Prednisone; Propylene Glycols; Protozoan Infections; Respiratory Tract Infections; Sepsis; Staphylococcal Infections; Transplantation Immunology; Transplantation, Homologous; Urinary Tract Infections; Virus Diseases

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Diagnosis, Differential; Female; Humans; Maxillary Sinus; Middle Aged; Natamycin; Nystatin; Radiography; Respiratory Tract Infections; Rhinitis; Sinusitis

Meningoencephalitis proved to be due to an amoeba (Naegleria) has been diagnosed in Great Britain for the first time. The first patient (a boy of 2) survived longer than any previously recorded cases, but in spite of early diagnosis and treatment he died 15 days after the onset of meningeal symptoms.Two other children who were exposed to the same possible source of infection (a warm, muddy puddle) had similar symptoms and developed mild meningitis. A naegleria was isolated from the cerebrospinal fluid of one of them. Both recovered after treatment with amphotericin.

Topics: Amebiasis; Amoeba; Amphotericin B; Autopsy; Brain; Child; Child, Preschool; Eukaryota; Humans; Male; Meningoencephalitis; Protozoan Infections; Respiratory Tract Infections; United Kingdom

Topics: Amphotericin B; Aspergillosis; Humans; Laryngeal Diseases; Male; Middle Aged; Nystatin; Respiratory Tract Infections

Topics: Actinomycosis; Adult; Amphotericin B; Biopsy; Blastomycosis; Coccidioidomycosis; Cryptococcosis; Diagnosis, Differential; Female; Histoplasmosis; Humans; Male; Middle Aged; Mycoses; Nystatin; Respiratory Tract Infections; Skin; Skin Diseases; Skin Ulcer; South America; Sputum

Topics: Aged; Amphotericin B; Diagnosis, Differential; Histoplasmosis; Humans; Male; Respiratory Tract Infections

Topics: Amphotericin B; Chronic Disease; Histoplasmosis; Humans; Pathology; Respiratory Tract Infections

Topics: Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Drug Therapy; Fungi; Histoplasmosis; Humans; Lung Diseases, Fungal; Respiratory Tract Infections; Toxicology

Topics: Abscess; Amphotericin B; Chronic Disease; Histoplasmosis; Humans; Lung Abscess; Pulmonary Surgical Procedures; Respiratory Tract Infections