amphotericin-b and Bacterial-Infections

Bacterial infections, caused predominately by Gram-positive and Gram-negative organisms, are proliferation of harmful strains of bacteria on or inside the body. Hospital-acquired and community-acquired bacterial infections have already put a heavy burden on the global health system. Antibiotics which can disrupt the processes necessary for bacterial cell growth and proliferation are effective weapons to fight against bacterial infections. However, the overuse and misuse of antibiotics have led to a rise in antibiotic resistance, creating an urgent need to develop novel antibiotics. 1,2,3-Triazole hybrids possess a broad spectrum of chemotherapeutic properties, also demonstrated promising in vitro and in vivo anti-bacterial activities. This review covers the recent (2000-2019) advances of 1,2,3-triazole hybrids as potential anti-bacterial agents. The structure-activity relationship (SAR) is also discussed for further rational development of 1,2,3-triazole hybrids with higher potency against both drug-sensitive and drug-resistant pathogens.

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Dose-Response Relationship, Drug; Humans; Microbial Sensitivity Tests; Molecular Structure; Structure-Activity Relationship; Triazoles

The management of neonatal sepsis is challenging owing to complex developmental and environmental factors that contribute to inter-individual variability in the pharmacokinetics and pharmacodynamics of many antimicrobial agents. In this review, we describe (i) the changing epidemiology of early- and late-onset neonatal sepsis; (ii) the pharmacologic considerations that influence the safety and efficacy of antibacterials, antifungals, and immunomodulatory adjuvants; and (iii) the recommended dosing regimens for pharmacologic agents commonly used in the treatment and prevention of neonatal sepsis. Neonatal sepsis is marked by high morbidity and mortality, such that prompt initiation of antimicrobial therapy is essential following culture collection. Before culture results are available, combination therapy with ampicillin and an aminoglycoside is recommended. When meningitis is suspected, ampicillin and cefotaxime may be considered. Following identification of the causative organism and in vitro susceptibility testing, antimicrobial therapy may be narrowed to provide targeted coverage. Therapeutic drug monitoring should be considered for neonates receiving vancomycin or aminoglycoside therapies. For neonates with invasive fungal infections, the development of new antifungal agents has significantly improved therapeutic outcomes in recent years. Liposomal amphotericin B has been found to be safe and efficacious in patients with renal impairment or toxicity caused by conventional amphotericin B. Antifungal prophylaxis with fluconazole has also been reported to dramatically reduce rates of neonatal invasive fungal infections and to improve long-term neurodevelopmental outcomes among treated children. Additionally, several large multicenter studies are currently investigating the safety and efficacy of oral lactoferrin as an immunoprophylactic agent for the prevention of neonatal sepsis.

Topics: Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Bacteremia; Bacterial Infections; Drug Monitoring; Fungemia; Humans; Infant; Infant, Newborn; Mycoses

Despite the relative high frequency of Candida bloodstream infection, Candida endocarditis is a rare entity. We report five cases of Candida endocarditis admitted to our hospital in the period between 2005 and 2011. Two cases were caused by C. albicans, two cases were caused by C. parapsilosis and in the last one, we didn't identify the species of Candida. All but one had clear risk factors for candidemia. Treatment consisted of amphotericin B with / without flucytosine in four patients, and they all underwent surgery for valve replacement and / or removal of intravascular devices. Overall mortality was 60% (40% of mortality was directly related to endocarditis). All patients who survived were given suppressive therapy with fluconazole for a minimum of two years.After stopping fluconazole there was a case of recurrence.

Topics: Acute Kidney Injury; Adult; Aged; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Bacterial Infections; Candida; Candidiasis; Carcinoma, Transitional Cell; Combined Modality Therapy; Disease Susceptibility; Drug Therapy, Combination; Endocarditis; Fatal Outcome; Female; Fluconazole; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Humans; Immunosuppressive Agents; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Pacemaker, Artificial; Postoperative Complications; Pregnancy; Pregnancy Complications, Infectious; Rheumatic Heart Disease; Sjogren's Syndrome; Spain; Tertiary Care Centers; Urinary Bladder Neoplasms

Amphotericin B is a polyene macrolide derived from Streptomyces nodosus. Introduced into therapy in 1957, for decades amphotericin B has been the "gold standard" for fighting systemic fungal infections. In order to facilitate its systemic use, much attention has been paid to the development of pharmaceutical forms that could reduce its toxicity, especially for the kidney. Because of its low solubility in water and excellent solubility in lipids, amphotericin B is an ideal candidate for lipid-based formulations. Three different lipid formulations for intravenous infusion are currently commercially available: liposomal amphotericin (AmBisome), Amphotericin lipid complex (Abelcet) and Amphotericin colloidal dispersion (Amphocil). The three lipid formulations of amphotericin B show significantly different structural, physical, chemical, pharmacokinetic, pharmacodynamic and toxicological characteristics. Several lines of evidence indicate that the three formulations of amphotericin B are not therapeutically equivalent. First, they are not bioequivalent. Second, even though a complete picture of controlled clinical research designed to compare effectiveness and safety of the three lipid formulations is not available, all the clinical studies analyzed report clear differences in toxicity between the three formulations. AmBisome appears to be clearly less toxic than the other two formulations, in terms of nephrotoxicity and of incidence of infusion-related adverse events. Third, the therapeutic non-equivalence of the three lipid formulations of amphotericin B is further supported by statements of Conferences and Scientific Societies that in their recommendations have awarded different grading to the three lipid formulations. (www.actabiomedica.it).

Topics: Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Chemistry, Pharmaceutical; Drug Carriers; Drug Compounding; Humans; Infusions, Intravenous; Lipids; Therapeutic Equivalency

The recent development of liposomal formulations compatible with aerosol delivery has expanded the potential to utilise chemotherapeutic agents directly targeted to the lungs more effectively. These are agents that would otherwise not be used because of their low solubility or toxicity. Various properties of liposomal carriers, including size, surface charge, composition and the presence of ligands, alter their efficacy and specificity towards alveolar macrophages to a great extent. This editorial summarises the advances in liposome-based drug delivery to alveolar macrophages.

Topics: Administration, Inhalation; Aerosols; Amphotericin B; Animals; Antifungal Agents; Antitubercular Agents; Bacterial Infections; Drug Carriers; Drug Delivery Systems; Liposomes; Lung Diseases, Fungal; Macrophages, Alveolar; Mice; Rats; Tuberculosis

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

Fever is associated with malignancy and is a common problem in cancer patients. Fever in the cancer patients is closely linked with infection, especially when the patient is granulocytopenic. When fever appears, a series of diagnostic and therapeutic measures must be taken even if precise knowledge of the cause of the infection is lacking. Fever can be caused by infection or by the cancer itself through tumor-related necrosis, hemorrhage or pyrogens. Infection is the more common cause, however. Bacterial and fungal sepsis can coexist and the bacteremia can overshadow the more difficult to determine fungal infection. For this reason it has become accepted practice to administer amphotericin B to granulocytopenic patients who remain febrile after a few days of broad-spectrum antimicrobial therapy and in whom no bacteria can be documented. Viral infection is rarely diagnosed in neutropenic patients without concomitant immunosuppression.

Topics: Amikacin; Amphotericin B; Bacteremia; Bacterial Infections; Ceftazidime; Clinical Trials as Topic; Drug Therapy, Combination; Fever; Fever of Unknown Origin; Humans; Mycoses; Neoplasms; Neutropenia; Vancomycin; Virus Diseases

Topics: Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Ganciclovir; Humans; Immunocompromised Host; Mycoses; Pneumonia; Pneumonia, Pneumocystis; Pneumonia, Viral; Trimethoprim, Sulfamethoxazole Drug Combination

Antibacterial therapy in chronic granulomatous disease requires antimicrobials active on Staphylococcus aureus and enterobacteria, which also have a good intracellular penetration and activity as rifampicin, fluoroquinolone, fosfomycin, cotrimoxazole. Several trials showed that cotrimoxazole was effective for the prevention of bacterial infection: thus, this antimicrobial can be used as long-term and continuous prophylaxia. Fungal infections require the use of amphotericin B. The place of new imidazole compounds as itraconazole should be assessed.

Topics: Amphotericin B; Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Infections; Drug Combinations; Granulomatous Disease, Chronic; Humans; Mycoses; Premedication; Sulfamethoxazole; Trimethoprim

Persistent fever that is refractory to broad-spectrum antibacterials is common in neutropenic patients undergoing induction chemotherapy of acute leukemia. Clinical experience suggests that many of these patients are infected with fungi. Until recently, data supporting the role of empiric antifungal therapy in this setting were limited to small groups of patients or postmortem reports. Evolving evidence in larger patient populations supports data from smaller series: febrile neutropenic patients who have failed to respond to a 4- to 7-day course of broad-spectrum antibacterials may benefit from the early initiation of antifungal therapy. Patients with fungal colonization or pulmonary infiltrates and adult patients who have not received previous fungal prophylaxis may especially benefit from the early use of antifungal drugs. Amphotericin B has been the "gold standard" for empiric antifungal therapy, although the newer azoles may be useful in certain situations.

Topics: Acute Disease; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Antineoplastic Agents; Bacterial Infections; Clinical Trials as Topic; Fever; Humans; Leukemia; Mycoses; Neutropenia; Remission Induction

It appears that the use of antibiotic combinations, especially synergistic ones, is indicated for the management of gram-negative bacillary sepsis in granulocytopenic patients. Synergism is a valuable factor in increasing the serum bactericidal activity, which is highly likely to be important for a favorable outcome in these infections. The potential side effects of antimicrobial combinations should not deter clinicians from their use. The most frequently used combinations for gram-negative bacillary infections are those involving beta-lactams and aminoglycosides. Other potentially synergistic combinations exist as well; however, the clinical experience with these combinations is limited, and, as with double beta-lactam combinations, their potential for antagonism necessitates care when using them. Besides gram-negative bacillary sepsis in granulocytopenic patients, severe staphylococcal infections might represent an indication for the use of combination therapy, especially in patients with compromised mechanisms of defense against infection.

Topics: Agranulocytosis; Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Blood Bactericidal Activity; Drug Resistance, Microbial; Drug Synergism; Drug Therapy, Combination; Fever; Humans; Lactams; Mycoses; Sepsis; Staphylococcal Infections

Topics: Aminoglycosides; Amphotericin B; Anemia, Aplastic; Bacterial Infections; Bone Marrow Transplantation; Graft Survival; Graft vs Host Disease; Humans; Immunosuppression Therapy; Leukemia; Mycoses; Patient Isolation; Postoperative Complications; Sulfamethoxazole; Time Factors; Trimethoprim; Virus Diseases

Infection is the major cause of morbidity and mortality in children receiving anticancer therapy. Children who have severe neutropenia (neutrophil count less than 100/mm3) for longer than 2 weeks should receive oral antibiotic prophylaxis. At present, trimethoprim sulfamethoxazole in combination with either nystatin or amphotericin B is the best regimen for reducing the incidence of serious infections. Trimethoprim sulfamethoxazole is very effective in the prevention of Pneumocystis carinii pneumonitis. Clinicans will have to balance the advantages and disadvantages of prophylaxis in patients who are at risk for P. carinii pneumonitis.

Topics: Adolescent; Adult; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Candidiasis; Child; Compliance; Drug Combinations; Humans; Leukemia; Neoplasms; Neutropenia; Nystatin; Pneumonia, Pneumocystis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Amphotericin B; Ampicillin; Antifungal Agents; Bacterial Infections; Blood Transfusion; Bone Marrow Transplantation; Carbenicillin; Cephalothin; Diagnosis, Differential; Fever; Gentamicins; Humans; Infections; Leukemia; Leukocytes; Lymphoma; Methicillin; Mycoses; Patient Isolators; Penicillin Resistance; Pneumonia, Pneumocystis; Polymyxins; Sepsis; Toxoplasmosis; Virus Diseases

The safety and efficacy of early bacterial prophylaxis with piperacillin-tazobactam were prospectively evaluated in 51 autologous peripheral blood stem cell transplantation (PBSCT) recipients. The results were compared with those obtained in 51 control patients receiving oral fluoroquinolones in a retrospective matched-pair control study. Overall, 76% of the study group and 98% of the control group developed at least one febrile episode during neutropenia (P=0.002). Time from neutropenia to the first febrile episode (FFE) was significantly longer in the study group than in the control group (P=0.04). Once a febrile episode appeared, the duration of fever was significantly longer in cases than in controls (median of 5 and 2 days respectively, P<0.001), and led to a more frequent use of empirical amphotericin B (AmB), not statistically significant (P=0.13). However, the total time of antibiotic administration was significantly greater in the control than in the study group (P=0.05). The duration of AmB treatment shows a trend toward a longer duration in the control than in study group (P=0.2). Overall, 86% of the Gram-positive bacteremia and 85% of the Gram-negative bacteria were susceptible to the tested antibiotics. Our study suggests that a subgroup of patients could benefit from prophylaxis with piperacillin-tazobactam without increasing toxicity or bacterial resistance.

Topics: Adolescent; Adult; Aged; Amphotericin B; Bacteremia; Bacterial Infections; Female; Fever; Fluoroquinolones; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Male; Matched-Pair Analysis; Middle Aged; Neutropenia; Penicillanic Acid; Peripheral Blood Stem Cell Transplantation; Piperacillin; Piperacillin, Tazobactam Drug Combination; Premedication; Transplantation, Autologous

To determine the efficacy of selective decontamination of the digestive tract (SDD) in patients undergoing elective transplantation of the liver.. Randomized, double-blind, placebo-controlled study.. Two academic teaching hospitals.. Adult patients undergoing elective liver transplantation: 26 patients receiving SDD and 29 patients receiving a placebo.. Patients undergoing SDD were administered 400 mg of norfloxacin once daily as soon as they were accepted for transplantation. Postoperative treatment for this group consisted of 2 mg of colistin, 1.8 mg of tobramycin, and 10 mg of amphotericin B, four times daily, combined with an oral paste containing a 2% solution of the same drugs until postoperative day 30. Prophylactic intravenous administration of antibiotics was not part of the SDD regimen in this study. Control patients were given a similar regimen with placebo drugs.. The mean number of postoperative bacterial and fungal infections in the first 30 days after transplantation was the primary efficacy end point. Days on a ventilator, days spent in the intensive care unit, and medical costs were registered as secondary outcome variables.. Of the 26 patients undergoing SDD, 22 (84.5%) developed an infection in the postoperative study period; in the placebo group (n = 29), these numbers were not significantly different (25 patients, 86%). The mean number of postoperative infectious episodes per patient was also not significantly different: 1.77 (SDD) vs. 1.93 (placebo). Infections involving Gram-negative aerobic bacteria and Candida species were significantly less frequent in patients receiving SDD (p <.001 and p <.05). Total costs were higher in the group receiving SDD.. Selective decontamination of the digestive tract does not prevent infection in patients undergoing elective liver transplantation and increases the cost of their care. It does, however, affect the type of infection. Infections with Gram-negative bacilli and with Candida species are replaced by infections with Gram-positive cocci.

Topics: Adult; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Bacterial Infections; Decontamination; Digestive System; Double-Blind Method; Female; Humans; Liver Transplantation; Male; Mycoses; Norfloxacin; Postoperative Complications; Tobramycin

The purpose of this study was to test the comparative efficacy and toxicity of empiric gentamicin and ciprofloxacin, in combination with piperacillin, in febrile patients with treatment-induced neutropenia. Fifty patients were prospectively randomized to receive piperacillin plus gentamicin (PG), and 46 were randomized to receive piperacillin plus ciprofloxacin (PC). The groups were similar in age, sex, diagnosis, duration of neutropenia, and incidence of positive cultures. The two antibiotic regimens were associated with comparable rates of defervescence in the patients with gram-positive bacteremia. In the patients with gram-negative bacteremia and those with negative cultures, however, defervescence was more prompt in the PC group. In particular, 27% of the culture-negative patients on PC, compared to only 5% of those on PG, defervesced within 72 hr (P = 0.015). Because of the more prompt defervescence in the PC group, amphotericin B was used less frequently; 78% of the patients on PG compared with only 56% of those on PC were started on amphotericin B (P = 0.025). PC is an effective alternative to the more traditional PG for treatment of febrile neutropenic hosts who have not been given prophylactic quinolones. More important, PC appears to hasten defervescence compared with PG, especially in culture-negative patients and those with gram-negative bacteremia, and may decrease the necessity of additional antimicrobial agents such as amphotericin B.

Topics: Adult; Amphotericin B; Bacterial Infections; Ciprofloxacin; Drug Therapy, Combination; Female; Fever; Gentamicins; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Mycoses; Neutropenia; Piperacillin; Prospective Studies; Time Factors; Vancomycin

The results are presented of two preliminary studies conducted to assess the role of GM-CSF as adjuvant treatment in neutropenic patients with bacterial or fungal infections. In the first study the effect of GM-CSF on the rate of response to antibiotics was assessed. Febrile neutropenic patients (n = 91) were randomized to receive ticarcillin-clavulanate plus netilmicin with or without GM-CSF (60 micrograms/m2). Response rates were significantly higher in patients who received antibiotics plus GM-CSF (p = 0.05). An increase in neutrophil count was seen in 89% of GM-CSF patients with initial low neutrophil counts (< 100/microliters) compared with 67% of control patients (p = 0.04). In the second study the activity of GM-CSF in patients with fungal infections was assessed. Neutropenic patients with documented fungal infections received amphotericin B plus GM-CSF. Of the eight evaluable patients, six responded and four had a complete response to treatment. The neutrophil counts of the two non-responding patients did not increase substantially during GM-CSF treatment and both died of their fungal infection. The prognosis of neutropenic patients with fungal infections is usually poor and the results of this pilot study are therefore very encouraging. The two studies show that GM-CSF is able to stimulate neutrophil recovery in neutropenic patients and may improve the response to antibiotic and antifungal treatment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Drug Therapy, Combination; Female; Fungemia; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Male; Middle Aged; Neutropenia; Prospective Studies; Treatment Outcome

The efficacy of an antimicrobial regimen for prevention of infections was prospectively evaluated in 113 patients undergoing autologous bone marrow transplantation (BMT). Ciprofloxacin, 500 mg orally twice a day plus antifungal prophylaxis, fluconazole 50 mg once daily plus amphotericin B tablets or suspension and tablets, each 200 mg four times a day, was given. In addition all patients received streptococcal prophylaxis for 10 days after BMT. Documented infections occurred in 39% (44 of 113) of patients and unexplained fever in 27% (30 of 113). The efficacy of this regimen was reflected in a low mortality rate (3.5%) from infections and in the low need for intravenous amphotericin B (7%). No benefit of protective isolation was found in 59 patients compared with 54 patients treated without isolation measures.

Topics: Adolescent; Adult; Amphotericin B; Bacterial Infections; Bone Marrow Transplantation; Ciprofloxacin; Drug Therapy, Combination; Female; Fluconazole; Humans; Male; Middle Aged; Mycoses; Patient Isolation; Prospective Studies; Transplantation, Autologous

To evaluate the efficacy of the technique of selective decontamination of the digestive tract in preventing the development of secondary infection and its influence on morbidity and mortality rates in multiple trauma patients with chest injuries requiring intermittent positive-pressure ventilation.. Prospective, double-blind, randomized study.. A multidisciplinary respiratory intensive care unit (ICU) in a 1,500-bed teaching hospital.. Seventy-two patients (mean Injury Severity Score of 29.5) who were intubated for > 48 hrs and remained in the ICU for > 5 days.. Patients were randomized on admission to receive selective decontamination therapy or placebo. All patients received intravenous cefotaxime for 72 hrs and the treatment group received oral and enteral selective decontamination with amphotericin B, polymyxin E, and tobramycin (n = 39), while the placebo group received a placebo containing oral paste and enteral solution (n = 33).. Secondary infection was determined clinically and microbiologically and surveillance cultures were monitored for gastrointestinal colonization.. The patient groups were fully comparable for age, severity of illness, and compromising factors. There was no difference in the number of patients infected (11 treatment group vs. 11 placebo), infections (17 vs. 16) and deaths (5 vs. 3); the duration of ICU (15.5 vs. 14.2 days) and hospital stays (26.3 vs. 25.5) were also similar. Microbiological surveillance cultures confirmed effective elimination of aerobic Gram-negative bacilli, and infections in the treatment group were largely due to Staphylococcus aureus and Staphylococcus epidermidis.. We have been unable to show any benefit from the use of selective decontamination of the digestive tract in the prevention of secondary infections in multiple trauma patients.

Topics: Adult; Amphotericin B; Bacterial Infections; Colistin; Double-Blind Method; Gastrointestinal Diseases; Humans; Injury Severity Score; Intensive Care Units; Intubation, Intratracheal; Length of Stay; Multiple Trauma; Prospective Studies; Tobramycin

The effect of a combination regimen using norfloxacin (NFLX) and amphotericin B (AMPH-B) for prevention of infections in patients with acute leukemia being treated by remission-induction chemotherapy in a randomized, controlled trial was studied. One hundred and six consecutive, evaluable patients were randomly assigned to receive orally 200 mg of norfloxacin two or four times daily and 200 mg of amphotericin B four times daily, or amphotericin B only. A smaller percentage of patients with bacteriologically-documented infections was observed in the study group compared with the control group (34.6% vs 56.9%; P < 0.05). The mean number of days that the patients received empirical antibiotic therapy was shorter in the study group (23 days vs 30 days; P < 0.05). The percentage of patients with a gram-negative bacterial infection (9.6% vs 27.5%; P < 0.05) or a fungal infection (17.3% vs 37.3%; P < 0.05) was decreased in the study group. This new combination antimicrobial regimen is safe and effective for prevention of gram-negative bacterial as well as fungal infections in patients with acute leukemia being treated with cytotoxic remission-induction chemotherapy.

Topics: Administration, Oral; Adult; Amphotericin B; Antineoplastic Agents; Bacterial Infections; Drug Combinations; Female; Fever; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Leukemia; Male; Middle Aged; Mycoses; Norfloxacin

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

To evaluate the use of selective decontamination of the digestive tract (SDD) (polymyxin, amphotericin, tobramycin, and intravenous cefotaxime) in a mixed intensive care unit, we performed a stratified, randomized, prospective study. The 331 patients were recruited over an 18-month period, with 256 patients remaining more than 48 hours. Stratification by acute physiology and chronic health evaluation (APACHE II) preceded randomization to control (standard antibiotic therapy) or treatment (SDD) groups. Nosocomial infection was significantly reduced in the SDD group (16.7%; 21 of 126 patients) compared with the control group (30.8%; 40 of 130 patients; p = 0.008). No difference was found in overall mortality rate or length of stay between the two groups. Those patients with admission APACHE II scores 10 to 19 demonstrated the most significant reduction in nosocomial infection (23 of 70 control vs 13 of 76 SDD; p = 0.03) and mortality (15 of 70 control vs 8 of 76 SDD; p = 0.07). Emergence of multiresistant microorganisms was not a clinical problem, but a definite change occurred in the ecology of environmental and colonizing bacteria. With the exception of cefotaxime, a reduction was noted in systemic antibiotic usage in the SDD group. We conclude that SDD is useful in selected patients in a mixed intensive care unit.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Bacterial Infections; Cefotaxime; Cost-Benefit Analysis; Critical Care; Cross Infection; Digestive System; Drug Therapy, Combination; Female; Humans; Length of Stay; Male; Middle Aged; Polymyxins; Prospective Studies; Tobramycin

In a prospective randomised study, the effects of two different colonisation prophylaxis techniques on colonisation and pulmonary infection were investigated in 40 critically ill patients with long-term ventilatory support (greater than or equal to 4 days). 20 patients were selectively decontaminated with 4 x 100 g polymyxin E, 4 x 80 mg tobramycin and 4 x 500 mg amphotericin B, administered through the gastric tube and with an antimicrobial sticky paste in the oropharynx (group I). 20 patients received 50 mg of polymyxin B and 80 mg of gentamicin dissolved in 10 ml of 0.9% saline at 6 h intervals into nose, oropharynx and stomach as well as 300 mg of amphotericin B in the oropharynx only (group II). All patients received cefotaxime systemically in the first 3 days. In group I gram-negative aerobic bacteria in the pharynx decreased from 35% to 0%, in group II from 40% to 10% and in the rectum from 80% to 61% (10% in the second week) in Group I and from 100% to 73% (33% in the second week) in group II. The decrease in gram-negative microorganisms was accompanied by an increase in the frequency of Staphylococcus epidermidis. In group I, two patients developed pneumonia and two patients urinary tract infections, in group II two patients suffered from pneumonia and 3 patients urinary tract infections. Both regimes are effective methods of prophylaxis for lowering colonisation with gram-negative aerobic bacteria and the frequency of pneumonia in patients requiring long-term mechanical ventilation. A possible selection of gram-positive bacteria must be appropriately monitored.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Cefotaxime; Colistin; Critical Care; Female; Gentamicins; Humans; Male; Middle Aged; Pneumonia; Polymyxin B; Prospective Studies; Respiration, Artificial; Time Factors; Tobramycin

To study the effect of enterally administered polymyxin E, tobramycin, and amphotericin B (selective flora suppression) on bacterial colonization, infection, resistance, and mortality rate.. Prospective, consecutive crossover controlled study.. Two surgical ICUs in a university hospital; ICU I with ten beds, ICU II with eight beds.. Two hundred patients entered the 1-yr trial. Fifty of 111 patients received selective flora suppression during the first 6 months in ICU I (test group), while 61 of 111 patients served as the control group in the following 6 months. In ICU II, 49 of 89 patients received no selective flora suppression in the first 6 months (control group), followed by 40 of 89 patients receiving selective flora suppression during the second 6-month period (test group).. The test group got a mixture of nonabsorbable antibiotics (paste and suspension) in the digestive tract. The control group received paste and suspension without antimicrobial agents. All 200 patients received cefotaxime during the first 4 days.. With the use of selective flora suppression, colonization with aerobic Gram-negative bacilli was significantly (p less than .01) reduced. There was also a significant reduction in nosocomial bronchopulmonary (ICU I and II; p less than .001) and urinary tract (ICU II; p less than .001) infections. The difference in mortality was not significant. There was no development of resistance against the antibiotics used during the limited period evaluated.. Selective flora suppression is effective in reducing secondary colonization by aerobic Gram-negative bacilli. Reduction of bronchopulmonary and urinary tract infections most likely occurs with colonization prevention.

Topics: Administration, Oral; Adult; Aged; Amphotericin B; Bacterial Infections; Bronchopneumonia; Colistin; Critical Care; Cross Infection; Female; Gram-Negative Aerobic Bacteria; Humans; Intensive Care Units; Male; Middle Aged; Mortality; Mouth; Ointments; Prospective Studies; Sepsis; Suspensions; Tobramycin; Urinary Tract Infections

Thirty-three (0.7%) of 4,818 trauma patients admitted between January 1, 1987, and July 1, 1989, developed invasive candidosis requiring IV antifungal therapy. All patients were seriously traumatized. Before developing candidosis, all patients had documented bacterial infections. These infections were generally polymicrobial and were treated with multiple broad-spectrum antibiotics (an average of 5.4 antibiotics for 17.2 days). Twenty-eight (85%) of 33 patients received enteral feedings for an average of 11 days +/- 1.5 (SEM) before developing candidosis and 24 (73%) received NG/oral nystatin for an average of 7.6 days +/- 0.9 before developing candidosis. All patients with candidosis were treated with intravenous amphotericin B: cumulative dose of 157.3 mg +/- 31.3 mg given over 10 days +/- 1.1. One patient developed recurrent candidosis despite NG/oral prophylaxis and enteral feedings. Six patients (18%) died due to sepsis and multiple organ failure. The patients who died did not objectively differ from the survivors. Candidosis is an infrequent infection in severely injured patients. Candidosis was invariably preceded by treatment with multiple broad-spectrum antibiotics for a variety of polymicrobial bacterial infections. NG/oral nystatin and enteral feedings did not prevent candidosis, in contrast to widely accepted beliefs. Amphotericin B therapy was safe. Recurrent candidosis was unusual. Candida infections had a high mortality rate associated with multiple blood transfusions and prolonged hospitalization. Candidosis represents a sign of severe injury and illness but can be amenable to prompt, aggressive treatment.

Topics: Adult; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Candidiasis; Female; Humans; Male; Middle Aged; Prospective Studies; Retrospective Studies; Wounds and Injuries

The question to be answered in this study was: Is prophylactic selective florasuppression advantageous compared to conventional antibiotic policy as far as microbial colonisation, infection, mortality and development of resistance are concerned? A prospective, consecutive, placebo-controlled study in two ICU's was carried out during four 6-months periods. 200 patients who were intubated for at least 3 days, required intensive care for a minimum of 5 days, and belonged to either class III or IV according to the "Therapeutic Intervention Scoring System" were included in the study. They received either placebo or the prophylaxis regimen described by Stoutenbeek et al., consisting of polymyxin E, tobramycin and amphotericin B. Oropharyngeal, tracheobronchial and rectal colonisation with aerobic gram-negative bacilli markedly decreased in the test groups. The rates of nosocomial bronchopulmonary infections (ICU I and II) and urinary tract infections (ICU II) were significantly reduced. There was no significant reduction in wound infection, septicaemia and mortality rates. No development of resistance and no increase of multi-resistant strains occurred. Selective florasuppression is effective in reducing infection rates in critically ill patients without development of resistant strains.

Topics: Adult; Aged; Amphotericin B; Bacterial Infections; Bronchopneumonia; Clinical Trials as Topic; Colistin; Cross Infection; Drug Therapy, Combination; Female; Humans; Intensive Care Units; Male; Prospective Studies; Risk Factors; Sepsis; Surgical Wound Infection; Tobramycin; Urinary Tract Infections

The ecologic effect of empiric systemic antibiotic therapy on the endogenous microflora was evaluated in 83 febrile granulocytopenic patients with cancer who were randomly allocated to receive moxalactam plus ticarcillin (45 patients) or tobramycin plus ticarcillin (38 patients) for suspected infection. Serial surveillance cultures of the nasal passages, oropharynx and feces performed twice a week showed that patients who received the former regimen had higher elimination rates and significantly lower acquisition rates (p = 0.027) for aerobic gram-negative bacilli than did patients who received the latter regimen. However, therapy with moxalactam plus ticarcillin also resulted in significantly higher acquisition rates for yeasts (p = 0.004). This was associated with a significantly higher fungal superinfection rate among these patients than among those who received tobramycin plus ticarcillin (40% v. 16%) (p less than 0.05). Moxalactam plus ticarcillin therapy created a greater microbial ecologic vacuum by the elimination of intestinal anaerobes, which, in turn, permitted fungal colonization and an increased risk of superinfection. Our results support the recommendation that an antipseudomonal penicillin plus an aminoglycoside be selected as empiric therapy for suspected infection in febrile granulocytopenic patients with cancer. Such a regimen would spare the anaerobic intestinal microflora, thereby reducing the risk of fungal colonization and infection.

Topics: Agranulocytosis; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Clinical Trials as Topic; Drug Therapy, Combination; Fever; Fungi; Gram-Negative Bacteria; Humans; Moxalactam; Mycoses; Ticarcillin; Tobramycin

Patients treated with cytotoxic therapy expected to produce neutropenia lasting two or more weeks were randomly assigned in a double-blind study to receive intravenous miconazole or placebo concomitant with empiric antibiotics to test whether miconazole can prevent fungal sepsis. The study drug was initiated at the time of first fever along with antibiotics and was continued until neutropenia resolved, fungal sepsis occurred, or persistent or recurrent unexplained fever after six or more days prompted substitution of the study drug by amphotericin B. Two hundred eight treatment courses in 180 patients were evaluated. Fungal sepsis occurred in only one patient receiving miconazole compared with eight patients receiving placebo (p = 0.03). Fatal fungal sepsis occurred in four patients receiving placebo and in none of the patients receiving miconazole (p = 0.08). There was no evidence for the development of resistance to polyenes or imidazoles in fungal isolates recovered from patients in this randomized trial or an increase in Aspergillus infections in patients who received miconazole in this randomized trial or in 121 subsequently treated patients who received unblinded use of miconazole. Thus, intravenous miconazole was more effective than placebo in preventing fungal sepsis in patients with chemotherapy-induced prolonged neutropenia.

Topics: Adolescent; Adult; Aged; Agranulocytosis; Amphotericin B; Bacterial Infections; Bone Marrow Transplantation; Child; Clinical Trials as Topic; Double-Blind Method; Humans; Injections, Intravenous; Miconazole; Middle Aged; Mycoses; Neutropenia; Random Allocation

Because gram-positive infections cause morbidity following intensive antileukemic chemotherapy, the effects of vancomycin versus placebo were evaluated in a randomized, double-blind, placebo-controlled trial in 60 adult patients with acute leukemia and first infectious fever during prolonged (mean of 32 days) granulocytopenia. Gram-positive sepsis was associated with first fever in 17 (28 percent) of the 60 patients. None of 31 patients randomly assigned to receive vancomycin demonstrated gram-positive infection, whereas 16 of 22 patients randomly assigned to receive placebo subsequently had gram-positive infection (seven had sepsis, and nine had local infections; p less than 0.005). All patients with gram-positive infection were then given vancomycin, and all showed prompt clinical responses. The predominant gram-positive organism causing infection was beta-lactam-resistant Staphylococcus epidermis (19 of 44 isolates). Patients randomly assigned to receive vancomycin had more rapid resolution of first infectious fever and fewer total febrile days during the granulocytopenic course than did patients randomly assigned to receive placebo. Although vancomycin had no effect on the presence or absence of documented fungal infection, patients treated with vancomycin received empiric amphotericin B for recurrent or persistent fever later (mean of 14 days after initial antibiotic coverage was begun) than did patients receiving placebo (mean of 9.9 days; p less than 0.005), and thus received fewer total days of empiric amphotericin B therapy (mean of 16.3 days) than did patients given placebo (mean of 24.6 days; p less than 0.01). These data demonstrate that empiric use of vancomycin reduces the morbidity of gram-positive infections following intensive antileukemic therapy and decreases the need for empiric use of toxic amphotericin B.

Topics: Adult; Agranulocytosis; Amphotericin B; Bacterial Infections; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Gram-Positive Bacteria; Humans; Leukemia; Middle Aged; Random Allocation; Vancomycin

To evaluate the possibility that in febrile granulocytopenic patients amphotericin B given along with granulocyte transfusions could increase the incidence of pulmonary complications, we studied 43 severely granulocytopenic patients during 46 episodes of fever. Granulocytes were administered as part of the clinical protocol to all 19 patients who had clinically or microbiologically documented infection; the other 24 patients were randomly allocated to treatment with granulocytes (13 patients) or without granulocytes (11 patients). In all, 32 patients received granulocyte transfusions during 35 episodes of fever. Pulmonary complications developed in six patients in each of the two randomized groups. The incidence of pulmonary complications was not influenced by the number of granulocyte transfusions or by the number of granulocytes per transfusion. Pulmonary complications were significantly more likely to occur in patients with fungal infections. Amphotericin B was given according to clinical indications; 21 patients in all received it. Survival was significantly poorer in patients with pulmonary complications, but the administration of amphotericin B was not related either to survival or to the incidence of pulmonary complications. We conclude that pulmonary complications and poor prognosis are related to underlying pulmonary fungal infection and not to any interaction between amphotericin B and granulocyte transfusions.

Topics: Adult; Aged; Amphotericin B; Bacterial Infections; Female; Granulocytes; Humans; Lung Diseases; Male; Middle Aged; Mycoses; Transfusion Reaction

In a prospective study the efficacy of two regimens for selective decontamination of the digestive tract was studied in patients with acute leukaemia during remission induction therapy. Seventy-eight patients were randomized to receive either a combination of cotrimoxazole, polymyxin B and nystatin (group A) or a combination of nalidixic acid, polymyxin B, neomycin and nystatin. With both regimens the gastrointestinal tract could be decontaminated equally effectively from potential pathogens. In the oropharyngeal region the decontamination from Enterobacteriaceae was significantly better in group A (P less than 0.01). In both groups less than 10% of the acquired infections were caused by gram-negative bacilli and no gram-negative septicaemia occurred in either group. The median time interval until the first acquired infection was 17 days in group A and 36 days in group B, respectively (P less than 0.05). It is concluded that regimen A might be more effective than regimen B though both regimens prevent reliably severe gram-negative infections.

Topics: Acute Disease; Adolescent; Adult; Aged; Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Candidiasis; Cephalosporins; Enterobacteriaceae Infections; Female; Flucytosine; Humans; Leukemia; Male; Middle Aged; Oxacillin; Penicillins; Prospective Studies; Staphylococcal Infections; Streptococcal Infections

Infected walled-off pancreatic necrosis (WON) is associated with increased morbidity and mortality. Systemic antibiotics are the main treatment, but are associated with adverse reactions and risk of superinfections. This study evaluates the efficacy of local instillation of antibiotics into WON.. We performed a retrospective cohort study of all consecutive patients with infected WON, who were treated with endoscopic transmural drainage and necrosectomy (ETDN) at a tertiary referral hospital between 2012 and 2016. A total of 91 patients were included. Patients often received concomitant intravenous and local antibiotics. Local antibiotics were added to the irrigation fluid depending on microbiological findings. A beneficial response was defined as the eradication of a microbe on subsequent culturing. Univariable and multivariable logistic regression analyses were used to evaluate antimicrobial efficacy.. At the first drainage 81 (86%) patients had infected and 10 sterile WON. Among patients with bacterial infections, neither local nor systemic antibiotics were associated with the eradication of microbes between first and second culture. Between the second and third culture, the use of local antibiotics was associated with the eradication of microbes (OR, 2.54; 95% CI, 1.25-5.18; p = 0.01), but not systemic antibiotics (OR, 0.75; 95% CI, 0.38-1.38; p = 0.33). Twelve patients had fungal infections treated with local amphotericin B between first and second culture. The fungus was eradicated in all 12 patients.. Local instillation of antibiotics may be a promising supplement to systemic administration.

Topics: Administration, Intravenous; Adult; Aged; Aged, 80 and over; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Bacterial Infections; Cohort Studies; Drainage; Female; Humans; Male; Middle Aged; Mycoses; Pancreatitis, Acute Necrotizing; Retrospective Studies

The emergence of multidrug-resistant bacterial and fungal strains poses a threat to human health that requires the design and synthesis of new classes of antimicrobial agents. We evaluated bis(N-amidinohydrazones) and N-(amidino)-N'-aryl-bishydrazones for their antibacterial and antifungal activities against panels of Gram-positive/Gram-negative bacteria as well as fungi. We investigated their potential to develop resistance against both bacteria and fungi by a multi-step resistance-selection method, explored their potential to induce the production of reactive oxygen species, and assessed their toxicity. In summary, we found that these compounds exhibited broad-spectrum antibacterial and antifungal activities against most of the tested strains with minimum inhibitory concentration (MIC) values ranging from <0.5 to >500μM against bacteria and 1.0 to >31.3μg/mL against fungi; and in most cases, they exhibited either superior or similar antimicrobial activity compared to those of the standard drugs used in the clinic. We also observed minimal emergence of drug resistance to these newly synthesized compounds by bacteria and fungi even after 15 passages, and we found weak to moderate inhibition of the human Ether-à-go-go-related gene (hERG) channel with acceptable IC

Topics: Anti-Bacterial Agents; Antifungal Agents; Bacteria; Bacterial Infections; Candida albicans; Candidiasis; Cell Line; Drug Discovery; Drug Resistance, Multiple; Fungi; Humans; Hydrazones; Microbial Sensitivity Tests; Mycoses

The d-Phe-Pro β-turn of the cyclic β-hairpin antimicrobial decapeptide tyrocidine A, (Tyrc A) was substituted with the d-Phe-2-aminobenzoic acid (2-Abz) motif in a synthetic analogue (1). The NMR structure of 1 demonstrated that compound 1 retained the β-hairpin structure of Tyrc A with additional planarity, resulting in approximately 30-fold reduced hemolysis than Tyrc A. Although antibacterial activity was partially compromised, a single Gln to Lys substitution (2) restored activity equivalent to Tyrc A against S. aureus, enhanced activity against two Gram negative strains and maintained the reduced hemeloysis of 1. Analysis by transmission electron microscopy (TEM) suggested a membrane lytic mechanism of action for these peptides. Compound 2 also exhibits nanomolar antifungal activity in synergy with amphotericin B. The d-Phe-2-Abz turn may serve as a tool for the synthesis of structurally predictable β-hairpin libraries. Unlike traditional β-turn motifs such as d-Pro-Gly, both the 2-Abz and d-Phe rings may be further functionalized.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Bacteria; Bacterial Infections; Candida albicans; Candidiasis; Escherichia coli; Hemolysis; Humans; Models, Molecular; Staphylococcal Infections; Staphylococcus aureus; Tyrocidine

Cationic amphiphiles derived from aminoglycosides (AGs) have been shown to exhibit enhanced antimicrobial activity. Through the attachment of hydrophobic residues such as linear alkyl chains on the AG backbone, interesting antibacterial and antifungal agents with a novel mechanism of action have been developed. Herein, we report the design and synthesis of seven kanamycin B (KANB) derivatives. Their antibacterial and antifungal activities, along with resistance/enzymatic, hemolytic, and cytotoxicity assays were also studied. Two of these compounds, with a C12 and C14 aliphatic chain attached at the 6″-position of KANB through a thioether linkage, exhibited good antibacterial and antifungal activity, were poorer substrates than KANB for several AG-modifying enzymes, and could delay the development of resistance in bacteria and fungi. Also, they were both relatively less hemolytic than the known membrane targeting antibiotic gramicidin and the known antifungal agent amphotericin B and were not toxic at their antifungal MIC values. Their oxidation to sulfones was also demonstrated to have no effect on their activities. Moreover, they both acted synergistically with posaconazole, an azole currently used in the treatment of human fungal infections.

Topics: Animals; Anti-Bacterial Agents; Antifungal Agents; Bacteria; Bacterial Infections; Cell Line; Cell Survival; Drug Design; Drug Resistance, Microbial; Fungi; Hemolysis; Humans; Kanamycin; Mice; Mycoses; Surface-Active Agents

We describe the laboratory-confirmed etiologies of illness among participants in a hospital-based febrile illness cohort study in northern Tanzania who retrospectively met Integrated Management of Adolescent and Adult Illness District Clinician Manual (IMAI) criteria for septic shock, severe respiratory distress without shock, and severe pneumonia, and compare these etiologies against commonly used antimicrobials, including IMAI recommendations for emergency antibacterials (ceftriaxone or ampicillin plus gentamicin) and IMAI first-line recommendations for severe pneumonia (ceftriaxone and a macrolide). Among 423 participants hospitalized with febrile illness, there were 25 septic shock, 37 severe respiratory distress without shock, and 109 severe pneumonia cases. Ceftriaxone had the highest potential utility of all antimicrobials assessed, with responsive etiologies in 12 (48%) septic shock, 5 (14%) severe respiratory distress without shock, and 19 (17%) severe pneumonia illnesses. For each syndrome 17-27% of participants had etiologic diagnoses that would be non-responsive to ceftriaxone, but responsive to other available antimicrobial regimens including amphotericin for cryptococcosis and histoplasmosis; anti-tuberculosis therapy for bacteremic disseminated tuberculosis; or tetracycline therapy for rickettsioses and Q fever. We conclude that although empiric ceftriaxone is appropriate in our setting, etiologies not explicitly addressed in IMAI guidance for these syndromes, such as cryptococcosis, histoplasmosis, and tetracycline-responsive bacterial infections, were common.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Ampicillin; Anti-Infective Agents; Bacterial Infections; Ceftriaxone; Child; Cohort Studies; Cryptococcosis; Emergencies; Female; Gentamicins; Histoplasmosis; Humans; Infections; Macrolides; Male; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Bacterial; Respiratory Distress Syndrome; Shock, Septic; Tanzania; Tetracycline; Young Adult

In this paper we report the SAR studies of a series of N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)amide and N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)sulfonamide derivatives 6(a-o) and 7(a-o), were synthesized in good yields and characterized by (1)H NMR, (13)C NMR and mass spectral analyses. The preparation of the key intermediate highlights an optimized palladium catalyzed (Pd₂(dba)₃/RuPhos) Buchwald cross-coupling of intermediate 2 and 3. The newly synthesized compounds were evaluated for their in vitro antibacterial activity against Staphylococcus aureus, (Gram-positive), Escherichia coli and Klebsiella pneumoniae (Gram-negative), antifungal activity against Candida albicans, Aspergillus flavus and Rhizopus sp. and antitubercular activity against Mycobacterium tuberculosis H37Rv, Mycobacterium smegmatis, Mycobacterium fortuitum and MDR-TB strains. The synthesized compounds displayed interesting antimicrobial activity. The compounds 7d, 7f, 7h and 7n displayed significant activity against Mycobacterium tuberculosis H37Rv strain.

Topics: Amides; Anti-Infective Agents; Antitubercular Agents; Bacteria; Bacterial Infections; Fungi; Humans; Imidazoles; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Mycoses; Structure-Activity Relationship; Sulfonamides

Imidazolium salts (Im(+)-R(2)R(3)-Cl(-)) attached to the N,N'-bis(salicylidene)-(±)-trans-1,2-diaminocyclohexane (saldach) backbone (4a-f) have been designed and successfully applied for the synthesis of the corresponding mononuclear complexes with Mn(III) and Fe(III) ions. The molecular structures of the saldach ligands H2(R(1))2saldach(Im(+)-R(2)R(3)-Cl(-))2 (R(1) = H, tert-Bu, R(2) = H, Et, n-Bu, R(3) = H, Me) and their [M(III)Cl{(R(1))2saldach(Im(+)-R(2)R(3)-Cl(-))2}] (M = Mn, Fe) complexes have been established. The free ligands exist as the phenol-OH and not as the zwitterionic (imine)N-H(+)· · ·(-)O(phenol) tautomer. Antimicrobial activity of the target compounds revealed higher potent antibacterial activity against Salmonella aureus, B. subtilis while less effective against E. coli and C. albicans and inactivity against A. flavus. Compound (4d) and its Fe(III) complex (6d) exhibit remarkable extra-potent bactericidal activity.

Topics: Anti-Infective Agents; Bacteria; Bacterial Infections; Cyclohexylamines; Escherichia coli; Ferric Compounds; Fungi; Humans; Imidazoles; Mycoses; Salts

Two different series of N-substituted imidazolium oximes and their monoquaternary salts were synthesized and biologically tested with respect to their ability to inhibit growth a diverse panel of antibiotic susceptible Gram-positive and antibiotic resistant Gram-negative bacteria as well fungal strains. The newly synthesized compounds were analyzed by spectral studies to confirm their structure. The preliminary results showed that all compounds tested possess promising antimicrobial potential against both susceptible Gram-positive and antibiotic resistant Gram-negative isolates, exhibiting a wide range of MIC values from 0.14 to 100.0 μg/mL. The structure-activity relationship demonstrates that the p-methylphenyl and p-fluorophenyl groups in monoquaternary salts 6 and 7 attached directly to the imidazolium ring could be essential for observed remarkable inhibitory profiles against clinically important pathogens Pseudomonas aeruginosa (MIC=0.14 μg/mL) and Klebsiella pneumoniae (MIC=1.56 μg/mL). Furthermore, the broth microdilution assay was then used to investigate the antiresistance efficacy of compound 7 against fourteen extended-spectrum β-lactamase (ESBL)-producing strains in comparison to eight clinically relevant antibiotics. Compound 7 exhibited a remarkable antiresistance profiles ranging between 0.39 and 12.50 μg/mL against all of ESBL-producing strains, which leads to the suggestion that may be interesting candidate for development of new antimicrobials to combat multidrug resistant Gram-negative bacteria.

Topics: Anti-Infective Agents; Bacterial Infections; Drug Resistance, Multiple; Fungi; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Imidazoles; Microbial Sensitivity Tests; Mycoses; Oximes

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

Cutaneous mucormycosis (zygomycosis), with subcutaneous spreading and dissemination, in immunocompetent patients is an uncommon disease caused by species belonging to the fungal genera Apophysomyces, Rhizopus and Saksenaea, among others.. A case of necrotising fasciitis by Saksenaea vasiformis in an immunocompetent woman is described. The infection was acquired through a car accident resulting in multiple injuries affecting mainly her right arm. After the surgical reduction of fractures, skin lesions worsened and led to necrosis. The patient quickly developed a severe necrotising fasciitis with negative cultures at first. Despite the extensive surgical debridement and the aggressive antifungal treatment, the patient died. The histopathological study showed a fungal infection due to a fungus belonging to the Mucorales order, which was confirmed by culturing the clinical sample on Sabouraud agar, and identifying the species by cultures on Czapek-Dox agar, and sequencing of the ITS region of the ribosomal DNA.. This case confirm the presence of this fungus in Spain, the value of histopathology for the mucormycosis diagnosis, as well as the need to perform special cultures to facilitate their isolation and identification to the species level by the combined use of Czapek-Dox agar and sequencing of the ITS region.

Topics: Accidents, Traffic; Amphotericin B; Antifungal Agents; Arm Injuries; Bacterial Infections; Coinfection; Combined Modality Therapy; Fasciitis, Necrotizing; Fatal Outcome; Female; Fractures, Open; Humans; Immunocompetence; Middle Aged; Mucorales; Mucormycosis; Multiple Trauma; Mycology; Radius Fractures; Shock, Septic; Wound Infection

In an attempt to identify new potential lead as antimicrobial agent, twenty hybrids of marine bromopyrrole alkaloids with 1,3,4-oxadiazole were designed based on molecular hybridization technique and synthesized. Synthesized molecules were evaluated for their antibacterial, antifungal and antitubercular activities. Hybrids 5d, 5i, 5j and 5k exhibited equivalent antibacterial activity (MIC of 1.56 μg/mL) compared with standard drug ciprofloxacin against Staphylococcus aureus and Escherichia coli. Equal antifungal activity (MIC of 1.56 μg/mL) was shown by of hybrids 5j, 5k and 7d compared with standard Amphotericin-B. The inhibition of Mycobacterium tuberculosis at concentrations as low as 1.6 and 1.5 μg/mL by compounds 5f and 7d respectively indicates that these compounds can act as leads for development of newer anti-TB compounds.

Topics: Alkaloids; Anti-Infective Agents; Antitubercular Agents; Bacteria; Bacterial Infections; Fungi; Halogenation; Humans; Microbial Sensitivity Tests; Mycoses; Oxadiazoles; Pyrroles

Here is presented, a rare case of disseminated protothecosis in a 10-year-old boy with combined immunodeficiency, hitherto unreported from India. Even though it is difficult to diagnose clinically, observation of the sporangiospores within the sporangium in culture gives the accurate laboratory identification of Prototheca spp. In this patient, failure to eradicate the infection with amphotericin B and recurrence with olecranon bursitis along with skin lesions and splenomegaly was observed. Disseminated protothecosis in a child with combined immunodeficiency and failure to eradicate the infection with amphotericin B is reported.

Topics: Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Bursitis; Child; Humans; Male; Olecranon Process; Prototheca; Treatment Failure

Topics: Amphotericin B; Bacterial Infections; Digestive System; Humans; Intestinal Perforation; Male; Tobramycin

Topics: ABO Blood-Group System; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Bacterial Infections; Caspofungin; Drug Therapy, Combination; Echinocandins; Female; Fungemia; Fusarium; Graft Rejection; Histocompatibility; Humans; Immunocompromised Host; Immunosuppressive Agents; Lipopeptides; Liver Transplantation; Meropenem; Middle Aged; Teicoplanin; Thienamycins

Invasive aspergillosis (IA) is a severe complication of liver transplantation. Risk factors for IA after deceased donor liver transplantation (DDLT) have been presented in several reports, but are not well established for living donor liver transplant recipients. Here, a retrospective case-control study was performed. Five cases with IA were investigated after living donor liver transplantation (LDLT) between January 1999 and December 2002 at Kyoto University Hospital. For comparison, living donor liver transplant recipients without IA were taken as controls. These patients had undergone LDLT 1 month before or after each IA case and had the same survival times as the latter. We evaluated the clinical and laboratory findings for both groups up until their demise. Patients with IA after LDLT had a very poor prognosis. By univariate analysis, risk factors for IA were preoperative intensive care unit stay (P = 0.02) and preoperative steroid administration (P = 0.02). Preoperative steroid administration for fulminant hepatitis possibly predisposed to the development of IA after LDLT.

Topics: Adult; Amphotericin B; Anti-Bacterial Agents; Aspergillosis; Bacterial Infections; Cephalosporins; Female; Humans; Immunosuppression Therapy; Liver Cirrhosis; Liver Transplantation; Living Donors; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Risk Factors

This report describes the case of fungal sinusitis in severely immunocompromised 32-year-old male with common-type acute lymphoblastic leukemia who relapsed after autologous peripheral blood transplantation. Empirical therapy with antibiotics and conventional amphotericin B failed to resolve the infection. Following therapy with AmBisome his symptoms abated and significantly improved scan picture was seen.

Topics: Adult; Amphotericin B; Anti-Infective Agents; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Bacterial Infections; Combined Modality Therapy; Cytarabine; Cytomegalovirus Infections; Enterococcus faecalis; Fatal Outcome; Humans; Idarubicin; Immunocompromised Host; Immunoglobulins, Intravenous; Liposomes; Male; Mycoses; Peripheral Blood Stem Cell Transplantation; Pneumonia; Postoperative Complications; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Pseudomonas putida; Pulmonary Edema; Pyrimidines; Sinusitis; Staphylococcus epidermidis; Transplantation, Autologous; Triazoles; Voriconazole

Topics: Acute Disease; Amphotericin B; Antifungal Agents; Bacterial Infections; Humans; Leukemia, Myeloid; Mycoses; Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma

We sought to assess if leaving in place a previously inserted noncolonized or infected implantable catheter (IC) is associated with an increase in morbidity in patients undergoing autologous peripheral stem cell transplantation (APSCT). Medical records from all patients between March 1997 and January 2002 undergoing APSCT with an IC in place were reviewed. Case group (IC in place) was compared with a control group (no IC) from 6 days prior to 60 days after APSCT. In all, 43 cases were matched with 43 controls by underlying disease, age and sex. In both groups, duration of neutropenia and use of antimicrobial prophylaxis were comparable. Underlying malignancies were lymphoma (22/24), multiple myeloma (14/12), leukemia (3/3), and others (7/7) in case and control groups. Cases and controls had comparable rates of risk for fever, bloodstream infection, use of vancomycin and amphotericin B, and death, as well as comparable lengths of stay and readmissions. ICs were used in 20 of 43 patients. Using the IC did not significantly increase the risk of fever, bloodstream infection, length of stay, and/or readmissions after APSCT but was associated with increased use of antibacterial and antifungal agents. Leaving in place a previously inserted, noncolonized or infected IC did not increase morbidity in patients undergoing APSCT.

Topics: Adult; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Catheterization, Central Venous; Female; Hematopoietic Stem Cell Transplantation; Humans; Lymphoproliferative Disorders; Male; Middle Aged; Retrospective Studies; Transplantation, Autologous; Vancomycin

Topics: Adolescent; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Catheterization, Central Venous; Child; Child, Preschool; Drug Resistance, Bacterial; Fever; Humans; Infant; Meropenem; Neoplasms; Neutropenia; Prospective Studies; Thienamycins; Vancomycin

Topics: Amphotericin B; Bacterial Infections; Causality; Drug Resistance, Microbial; Drug Resistance, Multiple; Endocarditis; Glycopeptides; Humans; Mycoses

A case of chronic paranasal sinuses with recurrent polyposis caused by miscellaneous infection--fungal (Aspergillus, Candida) and bacterial (Staphylococcus aureus, Enterobacter, Streptococcus) is described. The patient underwent 5 times surgical treatment (polypectomies, sinus operations). Good result was achieved after 2-years application of itraconazole and local Amphotericin B.

Topics: Amphotericin B; Antifungal Agents; Bacterial Infections; Combined Modality Therapy; Drug Administration Schedule; Female; Humans; Itraconazole; Middle Aged; Mycoses; Paranasal Sinus Diseases; Polyps; Recurrence; Sinusitis; Treatment Outcome

Fungal infections are frequent following lung transplantation and are associated with high mortality and morbidity. The study aims at 1) reporting our experience with fungal infections after lung transplantation; 2) identifying statistically significant correlations between the occurrence of fungal infections and bacterial infections, cytomegalovirus disease, rejection and steroid therapy; 3) assessing whether the presence of fungal infection has an impact on long-term survival.. 60 lung transplant recipients were studied with respect to incidence, pattern of presentation and median time to presentation of fungal infection after the transplant. Correlation analysis of the variables of interest was undertaken in 30 patients who had a minimum follow-up of 1 year following transplant.. The prevalence of fungal infection was 44%; severe infections occurred in 5 patients (11%). The presence of Candida preoperatively was not associated with an increased risk of fungal infection. In a logistic regression analysis, a significant correlation was found between the occurrence of fungal infection and the following variables: respiratory bacterial infections (p = 0.0003), cytomegalovirus disease (p = 0.00001) and steroid therapy (p = 0.04). No statistically significant difference was found between patients who experienced a fungal infection and those who did not, either in univariate or multivariate survival analysis (p = 0.08).. 1) fungal infections are frequent in lung transplant recipients and may be severe in more than 10% of the cases; 2) the presence of fungi preoperatively is not a contraindication to transplantation: an antifungal prophylaxis is probably indicated in such cases postoperatively; we recommend the use of the less nephrotoxic liposomal Amphotericin B by aerosol route; 3) a statistically significant association exists between fungal infections and both steroid therapy and CMV disease; this suggests that a similar antifungal prophylaxis is indicated in these clinical circumstances; 4) the presence of fungal infection is not an independent prognostic factor of long-term survival.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Bacterial Infections; Cytomegalovirus Infections; Female; Graft Rejection; Humans; Incidence; Lung Diseases; Lung Diseases, Fungal; Lung Transplantation; Male; Middle Aged; Prevalence; Prognosis; Retrospective Studies; Risk Factors; Steroids

Bacterial sepsis remains a frequent complication after liver transplantation. We previously reported the results of a pilot study that suggested that low expression of HLA-DR on monocytes is a predictive marker for the occurrence of sepsis. We have studied the value of this marker in an additional cohort of patients, and have analyzed the relation of HLA-DR expression with the use of immunosuppressive agents. 20 adult liver transplantation patients were prospectively monitored during the first 4 weeks after transplantation. All were treated according to standard protocols. The percentage of monocytes expressing HLA-DR was measured by flow cytometry. In addition, the effects of incubation of monocytes with prednisolone in vitro on the expression of HLA-DR was determined in 7 healthy volunteers. Seven patients developed bacterial sepsis after a median 15 (range 10-20) days after transplantation. HLA-DR expression was significantly lower in these patients on days 7, 14, 21, and 28 after transplantation compared with non-septic patients. The percentage of HLA-DR positive monocytes was 30% or less, 3 (1-8) days before onset of sepsis. On day 7 after transplantation, HLA-DR expression on 50% or less of monocytes had a positive predictive value for sepsis of 71%, whereas the negative predictive value was 85%. Patients who developed sepsis received significantly more prednisolone. Incubation with prednisolone in vitro lowered the expression of HLA-DR in a dose-dependent manner. We conclude that low HLA-DR expression on monocytes is a marker for a high risk of subsequent sepsis in liver transplantation patients. This high risk may be (at least partly) related to the dose of prednisolone.

Topics: Adolescent; Adult; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Biomarkers; Drug Therapy, Combination; Female; HLA-DR Antigens; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Liver Transplantation; Lymphocytes; Male; Middle Aged; Monitoring, Immunologic; Postoperative Complications; Predictive Value of Tests; Prospective Studies; Sepsis

Sixty four episodes of bacteraemia that appeared during antimicrobial prophylaxis with an oral quinolone plus an azole in neutropenic cancer patients were compared with 128 cases of bacteraemia in a cohort of controls matched for age, sex, underlying disease, neutropenia and vascular catheter in situ to assess differences in aetiology, cost of therapy and outcome. Patients who received prophylaxis had breakthrough bacteraemias of a different aetiology compared with the control group: they had significantly fewer multiply-resistant strains (21.9 vs. 51.5, P < 0.04) and a longer afebrile neutropenic period (9.55 days vs. 4.1, P < 0.001). Patients who received prophylaxis also had bacteraemias that were significantly more frequently caused by viridans streptococci (9.4%, vs. 1.7%, P < 0.01), enterococci (15.6% vs. 7.2%, P < 0.05) and Stenotrophomonas maltophilia (17.2% vs. 3.4%, P < 0.01). The cost of antimicrobial therapy per case (37401 SKK (1091 USD) vs. 31808 SKK (899 USD), P < 0.05) was also significantly higher in cases than controls; however, the number of administered antibiotics (4.18 vs. 3.21 per case, P = NS) was similar in both groups. There were no differences in outcome between both groups. However patients who received prophylaxis had significantly longer periods of afebrile neutropenia (9.55 days vs. 4.1, P < 0.001) and bacteraemia developed later than in controls. Also, the incidence of polymicrobial bacteraemia caused by multiresistant strains was lower among cases (21.9 vs. 51.5, P < 0.04).

Topics: Amikacin; Amphotericin B; Antibiotic Prophylaxis; Bacteremia; Bacterial Infections; Case-Control Studies; Catheters, Indwelling; Ceftazidime; Drug Therapy, Combination; Enterococcus; Female; Fluconazole; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Neoplasms; Neutropenia; Ofloxacin; Retrospective Studies; Streptococcal Infections; Treatment Outcome; Vancomycin; Xanthomonas

To evaluate the effect of total bowel decontamination (TD) and selective bowel decontamination (SD) in a non-protective environment clinical and laboratory data of children treated for acute leukaemia between 1983 and 1991 were analysed retrospectively. From 1983 until 1989 34 patients [18 acute non-lymphoblastic leukaemia (ANLL) patients, 16 acute lymphoblastic leukaemia (ALL) patients] received TD and 31 patients (8 ANLL patients, 23 ALL patients) received SD from 1987 until 1991. TD consisted of colistin sulphate, neomycin, cephaloridine and amphotericin B orally as well as Orabase and sterilized food, while the patients were nursed in a single room. SD consisted of oral colistin sulphate, neomycin and amphotericin B. Those patients with ANLL were nursed in a single room; patients with ALL were nursed in a single room during remission induction therapy only. All patients except those with ANLL receiving TD received Pneumocystis carinii pneumonia prophylaxis with cotrimoxazole. Because the two groups were heterogeneous for diagnosis and chemotherapy the occurrence of fever (central body temperature at least 38.5 degrees C) and major infections (septicaemia of infections of the deep tissues or organs) were registered during periods of neutropenia (neutrophilic granulocytes < or = 500/mm3 for at least 8 days). Patients on TD had 55 periods of neutropenia, patients on SD 80. Patients on TD had 89.1 periods of fever/100 periods of neutropenia whereas patients on SD had 56.3. Also patients on TD had 27.3 major infections/100 periods of neutropenia whereas patients on SD had 11.3. Major infections predominantly consisted of septicaemia caused by gram-positive bacteria. We conclude that, in this study, TD in a non-protective environment does not offer better protection against major infections that SD in patients with ALL or ANLL.

Topics: Adolescent; Amphotericin B; Anti-Bacterial Agents; Bacteremia; Bacterial Infections; Carboxymethylcellulose Sodium; Cephaloridine; Cephalosporins; Child; Child, Preschool; Colistin; Drug Therapy, Combination; Food Handling; Gram-Negative Bacterial Infections; Humans; Infant; Intestines; Leukemia, Myeloid, Acute; Neomycin; Neutropenia; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Sterilization; Trimethoprim, Sulfamethoxazole Drug Combination

Intra-abdominal infections account for 15 percent of technical failures after pancreatic transplantation. Although some data are available about intra-abdominal bacterial infections, no study has analyzed the incidence, treatment, and outcome of intra-abdominal fungal infections.. We retrospectively studied 445 consecutive pancreatic transplantations--45 percent were simultaneous pancreatic and renal, 24 percent pancreatic after renal, and 31 percent pancreatic transplantations alone--in patients with Type I diabetes mellitus. Donors were cadavers in 92 percent and living relatives in 8 percent. Primary transplantations were done in 80 percent and retransplantation in 20 percent. Of these 445 pancreatic transplantations, 90 percent were bladder-drained, 9 percent enteric-drained, and 1 percent duct-injected. Only symptomatic patients with documented culture-positive intra-abdominal fungal infections were included.. Intra-abdominal fungal infections occurred after pancreatic transplantation in 41 (9.2 percent) of 445 patients. Donor age, but not recipient age, was a significant risk factor. The rate of infections was higher for enteric-drained (21 percent) than for bladder-drained (10 percent) transplantations; for organs donated by living relatives (16 percent) than for those from cadavers (9 percent); and for pancreatic after renal (12 percent) and simultaneous pancreatic-renal (11 percent) than for pancreatic-only (5 percent) recipients. The rate of intra-abdominal fungal infections was 6 percent for recipients who were given antifungal prophylaxis (fluconazole, 400 mg/day for seven days after transplantation) compared with 10 percent for those without prophylaxis. The one-year graft survival rate for recipients with infection was 17 percent compared with 65 percent for those without (p = 0.0001); the survival rate was 70 percent compared with 92 percent for patients with and without infection, respectively (p = 0.0007). In 22 percent of recipients, the infection resolved and graft function persisted; in 58 percent, the infection resolved after transplant pancreatectomy; and in 20 percent, death occurred despite transplant pancreatectomy. Recipients with sole fungal or fungal and bacterial infection (n = 41) were 50 percent less likely to recover with a functioning graft and had a risk of death that was three times higher (p < or = 0.05) than those with sole bacterial infection (n = 48).. Intra-abdominal fungal infections after pancreatic transplants are associated with high morbidity and mortality rates, significantly higher than for sole bacterial infections. In addition to aggressive treatment, including transplant pancreatectomy and reduction of immunosuppression, efforts must be made toward better prevention of intra-abdominal fungal infections.

Topics: Adult; Age Factors; Amphotericin B; Antifungal Agents; Bacterial Infections; Candidiasis; Diabetes Mellitus, Type 1; Female; Fluconazole; Graft Survival; Humans; Immunosuppressive Agents; Incidence; Kidney Transplantation; Male; Pancreas Transplantation; Postoperative Complications; Reoperation; Retrospective Studies; Risk Factors; Tissue Donors; Treatment Outcome

Topics: Adolescent; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Bone Marrow Transplantation; Child; Child, Preschool; Female; Humans; Infant; Male; Neomycin; Polymyxin B; Retrospective Studies; Transplantation, Homologous

The authors test antibiotic strategies aimed at either mitigating bacterial translocation from the gut or delivering antibiotics specifically concentrated by the pancreas for prevention of early secondary infection after acute necrotizing pancreatitis.. Infection currently is the principal cause of death after severe pancreatitis. The authors have shown that the risk of bacterial infection correlates directly with the degree of tissue injury in a rodent model of pancreatitis. Bacteria most likely arrive by translocation from the colon.. Severe acute necrotizing pancreatitis was induced in rats by a combination of low-dose controlled intraductal infusion of glycodeoxycholic acid superimposed on intravenous cerulein hyperstimulation. At 6 hours, animals were randomly allocated to five treatment groups: controls, selective gut decontamination (oral antibiotics and cefotaxime), oral antibiotics alone, cefotaxime alone, or imipenem. At 96 hours, surviving animals were killed for quantitative bacterial study of the cecum, pancreas, and kidney.. The 96-hour mortality (35%) was unaffected by any treatment regimen. Cecal gram-negative bacteria were significantly reduced only by the oral antibiotics. Pancreatic infection was significantly reduced by full-gut decontamination and by imipenem, but not by oral antibiotics or by cefotaxime alone. Renal infection was reduced by both intravenous antibiotics.. Early pancreatic infection after acute necrotizing pancreatitis can be reduced with a full-gut decontamination regimen or with an antibiotic concentrated by the pancreas (imipenem) but not by unconcentrated antibiotics of similar spectrum (cefotaxime) or by oral antibiotics alone. These findings suggest that 1) both direct bacterial translocation from the gut and hematogenous seeding interplay in pancreatic infection while hematogenous seeding is dominant at extrapancreatic sites and 2) imipenem may be useful in clinical pancreatitis.

Topics: Acute Disease; Administration, Oral; Amphotericin B; Animals; Bacteria; Bacterial Infections; Bacterial Physiological Phenomena; Cecal Diseases; Cefotaxime; Colistin; Disease Models, Animal; Drug Therapy, Combination; Imipenem; Injections, Intravenous; Kidney Diseases; Male; Necrosis; Pancreas; Pancreatic Diseases; Pancreatitis; Rats; Rats, Sprague-Dawley; Survival Rate; Tobramycin

A total of 59 febrile neutropenic episodes were retrospectively recorded at Hôtel-Dieu de France Hospital between August 1st 1991 and December 31st 1992. These episodes were recorded in 51 cancer patients. Median neutropenia was less than one week in 50% of the cases. The etiology of these fever was documented in 27 episodes (46%) and in 70% of the cases gram (-) rods were documented. B-Lactam and Aminoglycoside antibiotics were used in 34 episodes at the initial treatment of these patients. Success rate at this initial treatment or with a modification of the antibiotic therapy was recorded in 85% of the patients. Only 15% of the patients failed to this antibiotherapy, 2/3 of them had their disease in progression. The systemic use of Amphotericine E in those patients with prolonged febrile neutropenia and the concommitent use of growth factors in a sub-group of patients at high risk could lead to a higher success rate in these patients.

Topics: Adult; Agranulocytosis; Amphotericin B; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Female; Fever; Hospitalization; Humans; Male; Neoplasms; Retrospective Studies; Risk Factors

The efficiency of stored platelet transfusion was evaluated in terms of clinical status in 141 thrombocytopenic patients. In a paired prospective study in which fresh platelets were used as controls, clinical efficiency was assessed on the basis of the ability to increase platelet count (recovery) and the time to the next transfusion (D). In 48 clinically stable patients, recovery of fresh and stored platelets was similar (47% and 41%, respectively) and the interval to the next transfusion was D4 and D3. In contrast, 27 patients who had bacterial infections showed significantly different recoveries (24%/5%) and the interval to the next transfusion was D3/D1 for fresh and stored platelets respectively. Similarly, in 16 patients who were treated concurrently with amphotericin B, 18 other patients with graft-versus-host disease, nine with splenomegaly and four with veno-occlusive disease (VOD), fresh platelets performed better than stored platelets, showing recoveries of 27%/18%, 29%/15%, 16%/3% and 15%/2%. Furthermore, the need for retransfusion within 24 h was significantly increased with stored platelets. In 19 patients with anti-HLA alloimmunization who were transfused with HLA-matched fresh and stored apheresis platelet concentrate (APC), efficiency was similar (38%/36% and D4/D3). This study indicates that the storage induces an impressive decrease in the in-vivo platelet recovery and survival in patients with certain clinical conditions.

Topics: Adult; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Bacterial Infections; Blood Preservation; Female; Humans; Male; Platelet Count; Platelet Transfusion; Prospective Studies; Thrombocytopenia; Time Factors

To describe the incidence of acute renal insufficiency and identify potential risk factors associated with this adverse medical event.. A cohort analytic study of patients with documented or suspected bacterial pneumonia.. Nationwide survey of 74 acute care hospitals across the US.. A total of 1822 adult patients with documented or suspected bacterial pneumonia who were receiving a cephalosporin, penicillin, or an aminoglycoside were enrolled. Patients were excluded if the duration of antimicrobial therapy was < 3 days or if the pneumonia was judged to be nonbacterial.. Clinical pharmacists completed standardized data collection forms on all patients enrolled in the study. Information regarding patient demographics, concurrent illnesses and medications, antibiotic administration, representative laboratory data, and the occurrence of any adverse clinical event was specifically captured. Information regarding the development of acute renal insufficiency was targeted as an event to be captured.. Univariate and multivariate analyses were performed to identify significant risk factors for acute renal insufficiency. A subset analysis was similarly performed to identify risk factors associated with aminoglycoside-related acute renal insufficiency.. Of the patients enrolled in this study, 8.2 percent developed acute renal insufficiency. Risk factors for acute renal insufficiency included renal disease, aminoglycoside therapy, nosocomial pneumonia, elevated estimated creatinine clearance prior to study entry, cardiac arrest/shock, congestive heart failure, total duration of antibiotics > 7 days, clindamycin therapy, liver disease, and first-generation cephalosporin usage. Risk factors for aminoglycoside-related acute renal insufficiency identified via multiple logistic regression included amphotericin B, congestive heart failure, aminoglycoside trough concentration > 1.5 mg/L, and clindamycin therapy.. The risk factors identified for acute renal insufficiency suggest that severity of illness strongly influences the development of renal insufficiency. Theoretically, the results of this study could serve as a framework for developing risk prevention programs within individual hospitals. Specific risk factors could be identified for a patient population and risk factors that could be modified could then be targeted for intervention. This type of information can also assist clinicians in predicting the probability of the adverse event for a particular patient and subsequently minimizing this risk by initiating intense monitoring or modifying the drug regimen.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Cohort Studies; Female; Heart Failure; Humans; Incidence; Male; Middle Aged; Pneumonia; Population Surveillance; Risk Factors; United States

Because the use of fluconazole prophylaxis had been associated with an increased rate of Candida krusei infections at The John Hopkins Oncology Center, early empiric amphotericin B plus flucytosine were given to febrile neutropenic patients colonized by C. krusei. By this practice, the proportion of fungemias attributable to C. krusei was low (12.5%) in patients receiving fluconazole over a 6-month interval. However, Torulopsis (Candida) glabrata assumed a much higher proportion of fungemias (75%) among patients receiving fluconazole. In vitro susceptibility testing combined with this clinical experience suggests that some T. glabrata isolates are not susceptible to fluconazole and can cause breakthrough infections in patients receiving fluconazole.

Topics: Amphotericin B; Bacterial Infections; Bone Marrow Transplantation; Candida; Candidiasis; Fluconazole; Flucytosine; Humans; Leukemia; Microbial Sensitivity Tests; Neutropenia

To identify factors that may aid in the diagnosis and treatment of patients with malignant neoplasms in whom hepatic abscesses develop.. Retrospective review of medical records.. Thirty-seven oncology patients in whom hepatic abscesses developed at the National Cancer Institute, Bethesda, Md, between June 1954 and October 1989.. Among 37 cancer patients, bacterial abscesses developed in 17 and fungal abscesses developed in 20. Among the patients with bacterial abscesses, 12 (71%) had a solid-tissue malignant neoplasm, 10 (59%) had a prior invasive procedure, and six (35%) had prior chemotherapy. In comparison, among the patients with fungal abscesses, 15 (75%) had a hematologic malignant neoplasm and five (25%) had a solid-tissue malignant neoplasm (P2 = .014). Two patients with fungal abscesses (10%) had a prior invasive procedure (P2 = .004) and 19 (95%) had prior chemotherapy (P2 < .0001). As compared with fungal abscesses, bacterial abscesses were larger (P2 < .00001) and fewer (P2 = .004). Antibiotics and percutaneous or surgical drainage effectively treated bacterial abscesses. Amphotericin B usually eradicated hepatic fungal infections.. The results of this study reveal the importance of the clinical setting in the diagnosis of hepatic abscesses in cancer patients. Aggressive treatment of these abscesses is indicated and is frequently effective.

Topics: Adult; Aged; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Drainage; Female; Humans; Liver Abscess; Male; Medical Audit; Middle Aged; Mycoses; Neoplasms; Retrospective Studies; Risk Factors; Survival Rate

The purpose of selective decontamination of the digestive tract (SDD) is to eradicate potentially disease-producing micro-organisms from the oropharynx and gastro-intestinal tract of intensive care unit (ICU) patients, thereby reducing the incidence of nosocomial sepsis, particularly pneumonia. Microbial biofilms form on endotracheal (ET) tubes even when SDD is being administered and may represent a persistent focus for infection. The aim of this investigation was to determine the susceptibilities of organisms adherent to ET tubes to SDD antibiotics (amphotericin B, tobramycin and polymyxin) and to measure the concentrations of these agents in the tracheal aspirates of 11 patients who were being mechanically ventilated. Following extubation, a section was cut from the tip of each ET tube and any adherent microorganisms subsequently isolated were identified and their MICs determined. Samples of tracheal aspirate were obtained three hours after administration of the SDD regimen and the concentrations of the constituent antimicrobials were measured. Enterobacteriaceae were not recovered from any of the tubes but six strains of Staphylococcus aureus, three Pseudomonas spp., three enterococci and four yeasts were isolated. Wide variations in the concentrations of all antibiotics were observed and in many cases they were below the MICs for the organisms isolated. In particular, tobramycin concentrations were uniformly less than the median MIC for the S. aureus isolates and this may account for the predominance of Gram-positive bacteria adherent to the ET tubes. Microbial biofilms attached to these tubes may have a role in the pathogenesis of nosocomial pneumonia in ICU patients.

Topics: Amphotericin B; Bacteria; Bacterial Adhesion; Bacterial Infections; Colistin; Critical Care; Digestive System; Humans; Intubation, Intratracheal; Microbial Sensitivity Tests; Pseudomonas; Staphylococcus aureus; Tobramycin; Trachea

Between 1984 and 1986 six patients with acute respiratory failure (requiring ventilation for at least 3 days) complicating acute pancreatitis were managed on the intensive care unit (median ventilation period 6 days; range 3-41 days). Between 1987 and 1989 nine similar patients were managed (median ventilation period 35 days, range 4-69 days), and a regimen of enteral tobramycin, polymyxin and amphotericin to selectively decontaminate the digestive tract (SDD) was introduced. Five of six patients treated before 1987 had serious infections (three Gram-negative, one fungal), compared with only one of nine patients treated with SDD (P < 0.05). Clinical signs of sepsis were evident for 62% of the pre-SDD period, compared with 39% of the period during SDD therapy (P < 0.001). Systemic antibiotic prescribing was reduced in the SDD group; however, mortality remained unaffected with only two patients surviving pre-SDD and three during SDD treatment. SDD reduces infection rates and sepsis in patients with acute pancreatitis and may help to improve the prognosis of this life-threatening condition.

Topics: Acute Disease; Adult; Aged; Amphotericin B; Bacteremia; Bacterial Infections; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Pancreatitis; Polymyxins; Tobramycin

ST 789, a newly synthesized chemical characterized by an aminoacidic group joined to the N9 position of the hypoxanthine ring, has recently been shown to be endowed with immunomodulatory properties. In this study we tested ST 789 in vivo for protective effects in Cyclophosphamide-immunosuppressed CD1 mice experimentally infected with several bacterial and fungal pathogens. We found that immunosuppressed mice infected with either fungi or bacteria were significantly protected, as evaluated both by percent mortality and survival time, when treated with doses of ST 789 even as low as 0.2 mg/kg/day. We also observed a marked synergism when the mice were first treated with ST 789 and then additionally treated with subeffective doses of antibiotics such as Amphotericin B, Ceftazidime, and Gentamicin. Even though further studies are required to elucidate the mechanisms underlying the ST 789 effects, these results show that ST 789 is a very promising new immunomodulator whose therapeutic potential has yet to be fully exploited.

Topics: Adjuvants, Immunologic; Amphotericin B; Animals; Arginine; Bacterial Infections; Cyclophosphamide; Female; Hypoxanthines; Immune Tolerance; Male; Mice; Mice, Inbred BALB C; Mycoses

Fifty-three patients undergoing autologous bone marrow transplantation received antimicrobial prophylaxis with ciprofloxacin with or without erythromycin and low dose intravenous amphotericin B. Eight patients remained afebrile throughout the neutropenic period. All other patients had one or more febrile episodes. The median time to fever after the onset of neutropenia was 7 days. There were no gram-negative organisms isolated from blood cultures during any of these episodes whereas gram-positive organisms were isolated in 28. There was one death in this series associated with sepsis. The use of low-dose prophylactic parenteral amphotericin did not prevent the subsequent successful use of full dose amphotericin for antibiotic-resistant fever. Ciprofloxacin effectively prevents gram-negative sepsis. The addition of erythromycin does little to prevent gram-positive sepsis. The use of regimens with agents with activity against gram-positive organisms is appropriate initial treatment of all febrile neutropenic episodes.

Topics: Adolescent; Adult; Amphotericin B; Bacteremia; Bacterial Infections; Bone Marrow Transplantation; Ciprofloxacin; Drug Therapy, Combination; Erythromycin; Female; Humans; Male; Middle Aged; Mycoses; Neutropenia; Transplantation, Autologous; Vancomycin

Forty-five cases of systemic neonatal candidiasis were diagnosed over a 9-year period in a neonatal intensive care unit; 42 infants weighted less than 1.5 kg. All had been very ill with preceding bacterial sepsis and other complications of low birthweight. Where treatment was instituted the mortality was low (4 out of 39 dying) and complications of treatment were transitory. We therefore recommend diligent examination for the presence of this infection, and treatment with a combination of amphotericin B and 5-flucytosine.

Topics: Amphotericin B; Bacterial Infections; Birth Weight; Candidiasis; Cross Infection; Drug Therapy, Combination; Flucytosine; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Retrospective Studies

Topics: Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Drug Therapy, Combination; gamma-Globulins; Granulocyte Colony-Stimulating Factor; Granulocytes; Hematologic Diseases; Humans; Leukopenia; Mycoses; Sepsis

Topics: Adolescent; Adult; Aged; Amphotericin B; Bacterial Infections; Creatinine; Critical Care; Female; Fluorescent Antibody Technique; Gastrointestinal Diseases; Gastrointestinal Motility; Humans; Male; Middle Aged; Polymyxins; Tobramycin

Experimental transplantations of cadaver bone marrow (BMT) in beagle dogs were performed to evaluate the problems and potentials in a preclinical setting. The effectiveness of selective decontamination of the gut (SD) and gnotobiotic surveillance in preventing infections during longer aplastic periods was investigated. Three groups of dogs were compared. Group A: controls. Group B: dogs with BMT, without SD and irregular gnotobiotic surveillance. Group C: dogs with BMT, with SD and regular gnotobiotic surveillance. The intestinal colonization of normal healthy beagles shows similarities as well as dissimilarities to the human intestinal microflora. Aerobic potentially pathogenic organisms do not colonize the gut of healthy beagles under our keeping conditions. SD resulted in a significant decrease in infections with Escherichia coli and Plesiomonas. Infections with anaerobes, as well as bacterial infections of the respiratory tract were, however, not prevented. The intestinal colonization in dogs of group C with Clostridium difficile is another obvious effect of SD. The infections encountered during the study indicate the importance of the "take" for the clinical significance and outcome of intestinal colonization with potentially pathogenic organisms. In order to reduce the drug burden of BMT patients, we consider the elimination of routine SD after BMT not to be superior to gnotobiotic surveillance and germ-specific short term decontamination.

Topics: Amphotericin B; Animals; Bacterial Infections; Bone Marrow Transplantation; Digestive System; Dogs; Norfloxacin; Premedication

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

Topics: Acyclovir; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Herpes Labialis; Humans; Mouth Diseases; Mycoses; Neoplasms

Immunosuppressed burned patients receiving antibiotics for suppression of bacterial infection are ideal hosts for opportunistic fungi. Massive excision of burns with autograft and homograft coverage has radically changed the course of disease. Three hundred ninety-three patients were admitted to the Shriners Burns Institute, of whom 125 patients had fungus cultured during their hospitalization and 42 patients subsequently developed involvement of three or more organs. Twenty-one of the 42 patients developed Candida septicemia requiring amphotericin B or flucytosine therapy. The mean third-degree burn in patients with Candida septicemia was 65% total body surface area compared to three-organ involvement/no clinical sepsis at 38% mean third-degree burn. Patients developing candidemia did so during the first week postburn and 7 days after excision therapy. It is hypothesized that massive burns with immunosuppression are further suppressed by repeated surgical intervention, anesthesia, and perioperative use of broad-spectrum antibiotics, further predisposing these patients to early development of Candida septicemia. With early recognition of burn wound invasion by routine biopsies, wound swabs, and early amphotericin therapy, the mortality has been reduced to 14% compared to 60-90% reported in other series.

Topics: Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Burns; Candidiasis; Child; Flucytosine; Humans; Immune Tolerance; Opportunistic Infections; Retrospective Studies; Wound Infection

Topics: Adolescent; Adult; Aged; Amphotericin B; Bacterial Infections; Cefotaxime; Child; Child, Preschool; Drug Therapy, Combination; Enterobacteriaceae Infections; Humans; Infant; Middle Aged; Thoracic Injuries; Tobramycin

Identification of the cause and subsequent specific therapy are indicated for those prolonged or relapsing fevers that follow abdominal surgery. On rare occasions, these fevers can be attributed to potentially life-threatening occult infections, including maxillary sinusitis, acute cholecystitis, antibiotic-related pseudomembranous colitis, toxic shock syndrome, systemic candidiasis, and transfusion-related cytomegalovirus disease, malaria, and babesiosis. Early recognition and appropriate treatment of these infections relieve anxiety, reduce hospital costs, and increase patient survival rates.

Topics: Abdomen; Acute Disease; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Candidiasis; Cholecystitis; Clostridium Infections; Colitis; Fever; Foreign Bodies; Humans; Intubation, Gastrointestinal; Intubation, Intratracheal; Maxillary Sinus; Postoperative Complications; Shock, Septic; Sinusitis; Staphylococcal Infections; Transfusion Reaction

Topics: Acute Disease; Amphotericin B; Bacterial Infections; Digestive System; Drug Combinations; Humans; Leukemia; Leukocyte Count; Neomycin; Polymyxin B; Polymyxins; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Two series of patients with endophthalmitis were compared. In the group treated with antibiotics or fungistatics, only 1 eye (4.3%) could be salvaged, whereas in the group with pars plana vitrectomy and antibiotics or fungistatics, 7 eyes (33%) had adequate visual acuity afterwards.

Topics: Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Endophthalmitis; Humans; Injections; Mycoses; Oxytetracycline; Visual Acuity; Vitrectomy; Vitreous Body

Thirty-one immunocompromised patients (22 renal allograft recipients, 5 patients receiving chronic corticosteroid therapy, and 4 patients undergoing chemotherapy for acute leukemia) with significant dermatologic infection, excluding typical cellulitis and herpesvirus infections, were retrospectively identified over a 12-year period. Of these 31 patients, 15 (48%) had infection restricted to their skin, 6 (19%) appeared to have primary cutaneous infection that spread hematogenously to other parts of the body, 2 (6%) had infections of adjoining nasal tissue that spread to contiguous skin, and 8 (26%) appeared to have disseminated systemic infection that spread to the skin. In six of the eight patients with apparent secondary skin involvement, the development of the cutaneous lesion was the first clinical indication of disseminated infection. Eleven immunocompromised patients (35%) with bacterial infection of the skin or subcutaneous tissue were identified. These patients could be divided into three categories: leukemic patients with bacteremic gram-negative infection metastasizing to the skin (3 cases), renal transplant recipients with recurrent staphylococcal infection on and around the elbow ("transplant elbow") or streptococcal sepsis from a site of cellulitis (5 cases), and immunocompromised patients with opportunistic bacterial infection due to Nocardia asteroides or atypical mycobacteria (3 cases). Seventeen immunocompromised patients (55%) with fungal infection of the skin or subcutaneous tissue were identified. These included 12 patients with opportunistic fungal infection (Cryptococcus neoformans, 4 cases; Aspergillus species, 3 cases; Paecilomyces, 2 cases; Rhizopus species, 2 cases; and Candida tropicalis, 1 case) and 5 patients with extensive, confluent cutaneous dermatophyte infections. One patient with protothecosis and two patients with extensive papillomavirus infection were identified. Of these latter two cases, one had his immunosuppression discontinued, with clearing of his extensive warts; the other had confluent warts of the face and neck that subsequently underwent malignant degeneration to squamous cell carcinoma while chronic immunosuppressive therapy was continued.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adolescent; Adult; Aged; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Connective Tissue Diseases; Debridement; Dermatomycoses; Female; Humans; Immunosuppression Therapy; Infections; Male; Middle Aged; Mycobacterium Infections; Prototheca; Skin Diseases, Infectious

Topics: Amphotericin B; Anti-Bacterial Agents; Antiviral Agents; Bacterial Infections; Drug Therapy, Combination; Humans; Infant, Newborn; Pneumonia; Pneumonia, Pneumococcal; Pneumonia, Staphylococcal; Pneumonia, Viral

Two hundred thirty-five fungal infections occurred in patients with malignant diseases over a four-year period. One hundred eighty-eight were due to Candida species and Torulopsis glabrata and are reviewed herein. The frequency was highest in patients with acute leukemia (11.9 per 100 registrations) with a frequency of 0.8 per 100 registrations in all cancer patients at this institution. Three or more predisposing factors were present in more than 50 percent of the cases; antecedent myelosuppression, chemotherapy, and antibiotic therapy were most common. Blood cultures were positive in only 35 percent of patients with disseminated candidiasis. Twenty-nine of 55 patients (53 percent) had candidemia without identifiable organ infection recovered. Eleven were given no systemic antifungal therapy and recurrence of infection was documented in two patients. Only six (4.5 percent) of 133 patients with proved deep organ infections recovered. Respiratory failure was the clinical cause of death in 62 percent of patients. Clinical features, cultures, and serologic tests were usually of no assistance in establishing the diagnosis early in the course of the infection.

Topics: Acute Disease; Amphotericin B; Bacterial Infections; Bacteriological Techniques; Candida; Candidiasis; Cytomegalovirus Infections; Humans; Ketoconazole; Leukemia; Lymphoma; Miconazole; Mycoses; Neoplasms; Neutropenia

The widely accepted practice of empirically administering amphotericin B to immunocompromised patients with fever unresponsive to antibiotics poses a hazard to transplant recipients receiving immunosuppression with cyclosporine. Improved methods of Candida detection and less toxic antifungals are urgently needed, but in the interim, treatment regimens should require a greater index of suspicion before initiating amphotericin therapy in patients receiving cyclosporine.

Topics: Amphotericin B; Bacterial Infections; Blood Transfusion; Bone Marrow Transplantation; Candidiasis; Cyclosporins; Graft Rejection; Granulocytes; Humans; Kidney Diseases; Potassium; Transplantation Immunology; Washington

Topics: Adult; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Bone Marrow Transplantation; Gentamicins; Humans; Intestines; Male; Middle Aged; Postoperative Complications; Transplantation, Autologous

Topics: Agranulocytosis; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Blood Transfusion; Drug Therapy, Combination; Fever; Granulocytes; Humans; Neutropenia

Topics: Adult; Aminoglycosides; Amoxicillin; Amphotericin B; Ampicillin; Anti-Bacterial Agents; Bacterial Infections; Cephalosporins; Cytarabine; Dental Care; Doxycycline; Drug Interactions; Humans; Idoxuridine; Mycoses; Nystatin; Penicillins; Tetracyclines; Virus Diseases

Topics: Adolescent; Adult; Agranulocytosis; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Bacterial Infections; Carbenicillin; Cephalothin; Child; Child, Preschool; Drug Therapy, Combination; Fever of Unknown Origin; Gentamicins; Humans; Mycoses; Neoplasms; Prospective Studies; Random Allocation

The use of granulocyte transfusions in profoundly neutropenic patients has increased markedly in recent years. Whenever a pulmonary infiltrate develops during the course of these transfusions, the question arises as to what role the transfusions are playing and whether the transfusions should be discontinued to prevent pulmonary deterioration. We have analyzed our recent experience of 593 granulocyte transfusions in 93 patients. 18 patients (19%) developed respiratory compromise or pulmonary infiltrates at some time during the course of granulocyte transfusion. 6 of the 18 cases were reactions to the granulocytes while the remainder were due to fluid overload or other causes. The risk of pulmonary complications did not correlate with the development of cytotoxic leukocyte antibodies, length of transfusion, or concomitant use of Amphotericin. They appeared to be more common in patients with active sepsis. Acute life-threatening pulmonary reactions were rare. Patients receiving granulocyte transfusions should be monitored carefully for pulmonary infiltrates, but other cases should be sought before the transfusions are discontinued.

Topics: Acute Disease; Agglutination; Amphotericin B; Bacterial Infections; Bronchopulmonary Sequestration; Child; Child, Preschool; Granulocytes; Humans; Infant; Lung Diseases; Respiratory Distress Syndrome; Transfusion Reaction

Topics: Amphotericin B; Bacterial Infections; Child; Flucytosine; Humans; Infections; Mycoses; Neoplasms; Protozoan Infections; Virus Diseases

Topics: Adolescent; Adult; Amphotericin B; Bacterial Infections; Candidiasis, Vulvovaginal; Drug Combinations; Female; Genital Diseases, Female; Humans; Middle Aged; Pelvic Inflammatory Disease; Suppositories; Tetracycline; Vaginitis

Infections of children with malignant disease, especially of the lympho-reticular system, are characterized by their severity, with a high mortality, as a consequence of defective immunocompetence. According to the immunosurveillance theory, temporary immune defects could have even facilitated the malignant growth. The neoplastic disease itself contributes to the immunodeficiency by multiple mechanisms. The powerful cytostatic-cytocidal drugs reduce the immune response also, especially in the phases of bone marrow depression. Granulocytopenia shows the most significant correlation with the incidence of serious infections. The different forms of hospital infections have been reviewed and classified as 1. bacterial, fungal and, rarely, (but most dangerous) protozoal infections, 2. endogenous infections with the patient's own anaerobic intestinal flora and 3. viral infections. The perspectives of up-to-date chemotherapy and management of the immunodeficiency e.g. with leucocyte transfusions, and attempts to prevent infection are discussed.

Topics: Amphotericin B; Antineoplastic Agents; Bacterial Infections; Blood Transfusion; Child; Communicable Diseases; Cross Infection; Humans; Immunologic Surveillance; Immunosuppression Therapy; Leukocytes; Leukopenia; Miconazole; Mycoplasma Infections; Mycoses; Neoplasms; Nutrition Disorders; Nystatin; Patient Isolation; Protozoan Infections; Tetracyclines; Virus Diseases

Topics: Amphotericin B; Bacterial Infections; Dexamethasone; Endophthalmitis; Gentamicins; Humans; Injections; Mycoses; Vitreous Body

Topics: Amphotericin B; Ampicillin; Aspergillus fumigatus; Bacterial Infections; Erythromycin; Humans; Mycoses; Nystatin; Penicillin Resistance; Sinusitis; Tetracycline; Trimethoprim

Topics: Amphotericin B; Anaerobiosis; Anti-Infective Agents; Bacterial Infections; Flucytosine; Humans; Infection Control; Infections; Mycoses; Parasitic Diseases; Virus Diseases

Twenty-seven deep fungal infections developed in 22 of 171 patients following renal transplantation. These infections included cryptococcosis (ten), nocardiosis (seven), candidiasis (four), aspergillosis (two), phycomycosis (two), chromomycosis (one), and subcutaneous infection with Phialophora gougeroti (one). Twelve infections occurred in living-related and ten in cadaveric recipients. Nineteen of the 22 patients were male. Infections occurred from 0 to 61 months after transplantation. Complicating non-fungal infections were present concomitantly in 15 patients. Thirteen patients died, eight probably as a result of fungal infection. Appropriate diagnostic procedures yielded a diagnosis in 20 of 27 infections, and therapy was begun in 18 patients. Serologic, culture, and biopsy procedures useful in making rapid diagnoses are advocated in the hope of increasing survival.

Topics: Adolescent; Adult; Amphotericin B; Antibodies, Fungal; Aspergillosis; Bacterial Infections; Candidiasis; Cryptococcosis; Female; Flucytosine; Fungi; Histocompatibility Testing; Humans; Immunosuppression Therapy; Kidney Transplantation; Male; Middle Aged; Mycoses; Nocardia Infections; Phialophora; Postoperative Complications; Retrospective Studies

Topics: Adolescent; Adult; Air Movements; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Bacterial Infections; Bacteriuria; Child; Ear; Feces; Female; Gentamicins; Humans; Male; Middle Aged; Mycoses; Nose; Nystatin; Paromomycin; Patient Isolators; Pharynx; Polymyxins; Skin; Vagina; Vancomycin

Topics: Amphotericin B; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Infections; Candida albicans; Candidiasis; Escherichia coli; Escherichia coli Infections; Mice; Neomycin; Nystatin; Penicillins; Polymyxins; Staphylococcal Infections; Streptomycin; Tetracycline; Thiourea; Undecylenic Acids

Topics: Amphotericin B; Bacterial Infections; Catheterization; Cerebral Ventricles; Cerebrospinal Fluid; Cerebrospinal Fluid Shunts; Chronic Disease; Coccidioidomycosis; Cryptococcosis; Humans; Hydrocephalus; Injections, Spinal; Meningitis; Methods; Time Factors; Wound Infection

Topics: Amphotericin B; Anti-Infective Agents; Antifungal Agents; Bacterial Infections; Child; Drug Therapy, Combination; Griseofulvin; Humans; Iodides; Mycoses; Nystatin; Streptomycin; Sulfamethoxazole; Sulfonamides; Tetracycline; Tolnaftate; Trimethoprim; Vancomycin

Topics: Adolescent; Adult; Amphotericin B; Bacterial Infections; Drug Therapy, Combination; Gentamicins; Humans; Intestines; Kanamycin; Leukemia; Middle Aged

Topics: Acute Kidney Injury; Adolescent; Adult; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Colistin; Deafness; Endocarditis, Bacterial; Female; Humans; Kanamycin; Kidney; Kidney Function Tests; Male; Middle Aged; Pseudomonas Infections; Sepsis; Staphylococcal Infections; Streptococcal Infections; Urea; Vancomycin