amphotericin-b and Bacteremia

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

Kodamaea (Pichia) ohmeri is a yeast-like fungus that has recently emerged as an important etiologic agent of fungemia in immunocompromised patients. We report such a case in a premature neonate born at 29 weeks of gestation. Prior to developing fungemia, she had two episodes of bacterial sepsis on day 13 and day 32 due to Enterobacter cloacae and Staphylococcus epidermidis, respectively. Kodamaea ohmeri was repeatedly isolated from blood cultures and its identity was determined by phenotypic characteristics and sequencing of the ITS and D1/D2 regions of rDNA. The neonate was successfully treated with amphotericin B. The published cases of K. ohmeri fungemia reported in pediatric patients are reviewed highlighting its increasing importance as a bloodstream pathogen.

Topics: Amphotericin B; Antifungal Agents; Bacteremia; Communicable Diseases, Emerging; DNA, Fungal; DNA, Ribosomal; DNA, Ribosomal Spacer; Enterobacter cloacae; Female; Fungemia; Humans; Infant, Newborn; Microbial Sensitivity Tests; Molecular Sequence Data; Mycological Typing Techniques; Phylogeny; Saccharomycetales; Sequence Analysis, DNA; Staphylococcus epidermidis; Treatment Outcome

Invasive candidiasis and candidemia are frequently encountered in the nosocomial setting particularly in the intensive care unit (ICU).. To review the current management of invasive candidiasis and candidemia in non-neutropenic adult ICU patients based on a review of the literature and an European expert panel discussion.. Empiric and directed treatment for invasive candidiasis are predicated on the hemodynamic status of the patient. Unstable patients may benefit from broad-spectrum antifungal agents, which can be narrowed once the patient has stabilized and the identity of the infecting species is established. In stable patients, a more classical approach using fluconazole may be satisfactory provided that the patient is not colonized with fluconazole resistant strains or there has been recent past exposure to an azole (<30 days). In contrast, pre-emptive therapy is based on the presence of surrogate markers.

Topics: Amphotericin B; Antifungal Agents; Bacteremia; Candida albicans; Candidiasis; Fluconazole; Humans; Intensive Care Units

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

Selective digestive decontamination (SDD) and selective oropharyngeal decontamination (SOD) are effective in improving survival in patients under intensive care. In this study possible differential effects in surgical and non-surgical patients were investigated.. This was a post hoc subgroup analysis of data from a cluster-randomized multicentre trial comparing three groups (SDD, SOD or standard care) to quantify effects among surgical and non-surgical patients. The primary study outcome was 28-day mortality rate. Duration of mechanical ventilation, duration of intensive care unit (ICU) and hospital length of stay, and bacteraemia rates were secondary outcomes.. The subgroup analyses included a total of 2762 surgical and 3165 non-surgical patients. Compared with standard care, adjusted odds ratios (ORs) for mortality were comparable in SDD-treated surgical and non-surgical patients: 0·86 (95 per cent confidence interval 0·69 to 1·09; P = 0·220) and 0·85 (0·70 to 1·03; P = 0·095) respectively. However, duration of mechanical ventilation, ICU stay and hospital stay were significantly reduced in surgical patients who had SDD. SOD did not reduce mortality compared with standard treatment in surgical patients (adjusted OR 0·97, 0·77 to 1·22; P = 0·801); in non-surgical patients it reduced mortality (adjusted OR 0·77, 0·63 to 0·94; P = 0·009) by 16·6 per cent, representing an absolute mortality reduction of 5·5 per cent with number needed to treat of 18.. Subgroup analysis found similar effects of SDD in reducing mortality in surgical and non-surgical ICU patients, whereas SOD reduced mortality only in non-surgical patients. The hypothesis-generating findings mandate investigation into mechanisms between different ICU populations.

Topics: Administration, Oral; Amphotericin B; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacteremia; Cefotaxime; Cluster Analysis; Colistin; Critical Care; Cross Infection; Decontamination; Digestive System Diseases; Drug Combinations; Female; Hospital Mortality; Humans; Infusions, Intravenous; Intubation, Gastrointestinal; Length of Stay; Male; Middle Aged; Oropharynx; Pharyngeal Diseases; Respiration, Artificial; Tobramycin

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

Infection is still one of the leading causes of morbidity and mortality in severely burned patients. Evidence suggests that many of the responsible organisms are endogenous. Systemic antibiotic prophylaxis is not effective, and produces resistant strains of microorganisms. SDD has been postulated to be beneficial for controlling and decreasing infections in critically ill patients. Its efficacy in severely burned patients, however, remains controversial. In order to analyze the efficacy of selective decontamination of the digestive (SDD) tract, to decrease the bacterial colonization of the aerodigestive tract and burn wounds, and the incidence of septic complications in severely burned children, 23 pediatric patients affected of severe burns were prospectively randomized in a double-blinded study. Eleven patients received SDD (Polymyxin E, Tobramycin, and Amphotericin B), and 12 placebo. Demographics, hospital course, microbiology results, complications, infectious episodes, and serum levels of IL-1beta, IL-6, IL-10, and TNF-alpha were compared to determine the efficacy of SDD. Colonization rates to the wound, sputum, nasogastric aspirates, and feces were similar. Pneumonia, sepsis and other complications had similar incidence in both groups. Serum levels of all cytokines studied were also comparable, suggesting a similar inflammatory status in all patients, regardless of the treatment received. Patients in the SDD group, however, had a significantly higher incidence of diarrhea (P=0.003). We can conclude that selective decontamination of the digestive tract with Polymixin E, Tobramycin and Amphotericin B is not effective to decrease bacterial colonization and infectious episodes in severely burned pediatric patients.

Topics: Amphotericin B; Analysis of Variance; Bacteremia; Burns; Child; Cross Infection; Cytokines; Digestive System Diseases; Double-Blind Method; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Injury Severity Score; Intubation, Gastrointestinal; Linear Models; Male; Polymyxins; Probability; Prospective Studies; Reference Values; Survival Rate; Tobramycin; Treatment Outcome

The purpose of this study was to determine if patients with high vancomycin (VAN) serum levels experience more toxicity than underdosed patients with lower (VAN) levels, and whether low VAN serum levels cause therapeutic failures in patients with gram-positive bacteremia. In 198 cancer patients trough and peak serum levels of VAN were measured. Acute toxicity (Red Man syndrome) appeared in 3 patients (1.5%). Patients previously or currently treated with other nephrotoxic compounds (134 patients) presented the same incidence of nephrotoxicity as those receiving VAN for the first time in monotherapy (64 patients). VAN did not increase the toxicity when patients were dosed simultaneously or previously with aminoglycosides or amphotericin B. Our second observation, when studying serum levels in our 198 patients was that high VAN trough serum levels (trough > 15 microg/mL) were associated with significantly more nephrotoxicity (33.3% vs. 11.1%, P < 0.03) than low levels in the subgroups of either pretreated patients or unpretreated with other nephrotoxic drugs. None of 198 patients who had trough levels below 15 microg/mL had peak levels exceeding 40 microg/mL. This suggests that only serum monitoring of trough levels may predict nephrotoxicity. A case control study was conducted to compare a group of 22 VAN failures with 22 successfully treated patients matched in underlying disease and neutropenia who were treated in the same period, under the same antibiotic policy, at the same cancer center, for gram-positive bacteremia. Persisting, enterococcal, or mixed enterococcal plus staphylococcal bacteremia were the only statistically significant risk factors which predicted therapy failure in cancer patients. Neither peak nor trough VAN serum levels predicted failure or cure of gram-positive bacteremia in cancer patients.

Topics: Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Bacteremia; Case-Control Studies; Drug Resistance, Microbial; Drug Synergism; Drug Therapy, Combination; Humans; Kidney Diseases; Neoplasms; Neutropenia; Risk Factors; Slovakia; Vancomycin

Fungal infections are a major problem in patients with hematologic malignancy. Attempts to reduce their frequency with antifungal agents have not been successful. A double-blind, controlled, single-center trial was conducted with 96 consecutive patients undergoing 154 episodes of chemotherapy. Patients received 400 mg of fluconazole or placebo until bone marrow recovery or initiation of intravenous amphotericin B infusions. End points were amphotericin B use, fungal infection, stable neutrophil count > 0.5 x 10(9)/L, toxicity precluding further fluconazole use, and death. By Kaplan-Meier estimation, the time to initiation of amphotericin B therapy was shorter in 76 patients treated with placebo than in 75 treated with fluconazole (P = .003). Also, fluconazole reduced the number of febrile days by 20% (P = .002) and prevented oropharyngeal candidiasis (1/75 vs. 9/76, P = .018). The frequency of deep mycoses (8/76 vs. 8/75) and outcome were unaffected. Fluconazole did not have a favorable effect on infection-related health care costs and was associated with prolonged severe neutropenia (P = .01).

Topics: Adult; Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Aspergillosis; Bacteremia; Candidiasis, Oral; Double-Blind Method; Drug Therapy, Combination; Fever; Fluconazole; Humans; Incidence; Infusions, Intravenous; Leukemia; Lymphoma; Middle Aged; Mycoses; Neutropenia; Treatment Outcome

The efficacy and toxicity of teicoplanin and vancomycin in the initial empirical antibiotic regimen in febrile, neutropenic patients with hematologic malignancies were compared in a prospective, randomized, unblinded, multicenter trial in the setting of 29 hematologic units in tertiary-care or university hospitals. A total of 635 consecutive febrile patients with hematologic malignancies and chemotherapy-induced neutropenia were randomly assigned to receive intravenously amikacin plus ceftazidime plus either teicoplanin at 6 mg/kg of body weight once daily or vancomycin at 1 g twice daily. An efficacy analysis was done for 527 evaluable patients: 275 treated with teicoplanin and 252 treated with vancomycin. Overall, successful outcomes were recorded for 78% of patients who received teicoplanin and 75% of those who were randomized to vancomycin (difference, 3%; 95% confidence interval [CI], -10 to 4%; P = 0.33). A total of 102 patients presented with primary, single-agent, gram-positive bacteremia. Coagulase-negative staphylococci accounted for 42%, Staphylococcus aureus accounted for 27%, and streptococci accounted for 21% of all gram-positive blood isolates. The overall responses to therapy of gram-positive bacteremias were 92 and 87% for teicoplanin and vancomycin, respectively (difference, 5%; CI, -17 to 6%; P = 0.22). Side effects, mainly represented by skin rash, occurred in 3.2 and 8% of teicoplanin- and vancomycin-treated patients, respectively (difference, -4.8%; CI, 0.7 to 8%; P = 0.03); the rate of nephrotoxicity was 1.4 and 0.8% for the teicoplanin and vancomycin groups, respectively (difference, 0.6%; CI, -2 to 1%; P = 0.68). Further infections were caused by gram-positive organisms in two patients (0.7%) treated with teicoplanin and one patient (0.4%) who received vancomycin (difference, 0.3%; CI, -0.9 to 1.0%; P = 0.53). Overall mortalities were 8.5 and 11% for teicoplanin- and vancomycin-treated patients, respectively (difference, -2.5%; CI, - 2 to 7%; P = 0.43); death was caused by primary gram-positive infections in three patients (1%) in each treatment group. When used for initial empirical antibiotic therapy in febrile, neutropenic patients, teicoplanin was at least as efficacious as vancomycin, but it was associated with fewer side effects.

Topics: Adolescent; Adult; Aged; Amikacin; Amphotericin B; Bacteremia; Ceftazidime; Drug Therapy, Combination; Female; Fever; Gram-Positive Bacterial Infections; Hematologic Diseases; Humans; Male; Middle Aged; Neoplasms; Neutropenia; Prospective Studies; Teicoplanin; Vancomycin

Whether Candida within the patient microbiome drives the pathogenesis of Staphylococcus aureus bacteremia, described as microbial hitchhiking, cannot be directly studied. Group-level observations from studies of various decontamination and non-decontamination-based ICU infection prevention interventions and studies without study interventions (observational groups) collectively enable tests of this interaction within causal models. Candidate models of the propensity for Staphylococcus aureus bacteremia to arise with versus without various antibiotic, anti-septic, and antifungal exposures, each identified as singleton exposures, were tested using generalized structural equation modelling (GSEM) techniques with Candida and Staphylococcus aureus colonization appearing as latent variables within the models. Each model was tested by confrontation against blood and respiratory isolate data, obtained from 467 groups within 284 infection prevention studies. Introducing an interaction term between Candida colonization and Staphylococcus aureus colonization substantially improved GSEM model fit. Model-derived coefficients for singular exposure to anti-septic agents (- 1.28; 95% confidence interval; - 2.05 to - 0.5), amphotericin (- 1.49; - 2.3 to - 0.67), and topical antibiotic prophylaxis (TAP; + 0.93; + 0.15 to + 1.71) as direct effects versus Candida colonization were similar in magnitude but contrary in direction. By contrast, the coefficients for singleton exposure to TAP, as with anti-septic agents, versus Staphylococcus colonization were weaker or non-significant. Topical amphotericin would be predicted to halve both candidemia and Staphylococcus aureus bacteremia incidences versus literature derived benchmarks for absolute differences of < 1 percentage point. Using ICU infection prevention data, GSEM modelling validates the postulated interaction between Candida and Staphylococcus colonization facilitating bacteremia.

Topics: Amphotericin B; Anti-Bacterial Agents; Bacteremia; Candida; Cross Infection; Humans; Intensive Care Units; Staphylococcal Infections; Staphylococcus aureus

This study aimed to highlight the association of stellate neuroretinitis occurring secondary to endogenous candidemia.. We report an unusual presentation of endogenous Candida endophthalmitis as a stellate neuroretinitis in the setting of Cornelia de Lange syndrome.. A 34-month-old girl with severe Cornelia de Lange syndrome and a history of parenteral nutrition dependence requiring a chronic central venous catheter presented with bilateral endophthalmitis secondary to candidemia. In one eye, the endophthalmitis had the atypical presentation as a stellate neuroretinitis.. This case represents a unique association of stellate neuroretinitis secondary to Candida infection in a patient with Cornelia de Lange syndrome.

Topics: Administration, Ophthalmic; Amphotericin B; Antifungal Agents; Bacteremia; Candida albicans; Candidemia; Candidiasis; Child, Preschool; De Lange Syndrome; Endophthalmitis; Eye Infections, Fungal; Female; Humans; Intravitreal Injections; Klebsiella; Klebsiella Infections; Retinitis; Voriconazole

Here, we describe an invasive infection due to Trichosporon coremiiforme in an HIV positive patient with neutropenia. The strain was first erroneously identified as Trichosporon asahii by conventional methods, but correctly identified by mass spectrometry using matrix-assisted laser desorption/ionization time-of-flight technology (MALDI-TOF MS) and ribosomal DNA sequencing. The infection was successfully resolved after antifungal treatment with amphotericin B and fluconazole. This case report is a contribution to the study of T. coremiiforme infections and reinforces its relevance as a species capable of causing invasive human infection in immunocompromised patients and also contributes to the study of its susceptibility profile against antifungal drugs.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antitubercular Agents; Bacteremia; Catheter-Related Infections; Central Venous Catheters; Drug Therapy, Combination; Female; Fluconazole; HIV; HIV Infections; Humans; Immunocompromised Host; Middle Aged; Neutropenia; Trichosporon; Trichosporonosis; Tuberculosis, Pulmonary

Bloodstream Candida infection is a life-threatening event among ICU admitted patients. This infection is caused by a diverse range of Candida species having varied minimum inhibitory concentrations.. To identify Candida species causing bloodstream infections with their antifungal susceptibility determination.. Candida species isolated from the blood of ICU admitted patients were identified by phenotypic as well as by molecular methods including PCR-RFLP using MspI restriction enzyme and MALDI TOF MS. The minimum inhibitory concentration of fluconazole, voriconazole, amphotericin B and caspofungin was determined against isolated Candida species by CLSI M27A. A total of 119 Candida species were isolated. Among them, C. tropicalis(n=29) was the predominant isolate followed by C. parapsilosis(n=18), C. glabrata (n=12), C. krusei (n=11) and C. albicans(n=11). Uncommon Candida species isolated were; Wickerhamomyces anomalus(n=15), Kodaemia ohmeri(n=8), C. lusitaniae (n=5) and C. auris (n=2). A varied antifungal MIC values were observed. Caspofungin had the lowest MIC among the tested antifungals. Increased fluconazole MIC was observed against the isolated Candida species including C. tropicalis. All the isolated C. lusitaniae and C. auris strains have ≥1mcg/ml amphotericin B MIC. In comparison to fluconazole, voriconazole was more effective when tested in vitro.. Emergence of uncommon Candida species having varied antifungal MIC warns the physicians to have a prompt, accurate identification with antifungal MIC determination in each case of bloodstream Candida infections.

Topics: Amphotericin B; Antifungal Agents; Bacteremia; Candida; Candida tropicalis; Candidiasis; Caspofungin; Cross-Sectional Studies; Fluconazole; Humans; Intensive Care Units; Microbial Sensitivity Tests; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Voriconazole

Opportunistic infections, while well studied in the AIDS population, continue to have variable and surprising presentations. Here, we present a case of disseminated histoplasmosis with disseminated nontuberculous mycobacterial infection in a 50 year old man with long standing AIDS living in a non-endemic area.. Patient presented with a constellation of symptoms, and imaging of the chest showed a pulmonary mass with cavitation, multiple nodules, and ground glass opacities. Further investigations revealed granulomatous lung nodules and fungemia consistent with Histoplasma capsulatum, and coinfection with disseminated nontuberculous mycobateria in a nonendemic area.. Immunocompromised patients risk co-inhabitation by multiple infectious organisms. Some of these organisms may preside in the host for years prior to reactivation. Clinicians in non endemic areas should therefore be careful to not overlook specific organisms based on a lack of a recent travel history. Physicians in nonendemic areas should become more familiar with the clinical findings and diagnostic approach of infectious such as Histoplasmosis, to ensure earlier recognition and treatment in immunocompromised individuals.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-Bacterial Agents; Anti-HIV Agents; Antifungal Agents; Antitubercular Agents; Azithromycin; Bacteremia; California; Emtricitabine; Ethambutol; Fungemia; Heterocyclic Compounds, 3-Ring; Histoplasmosis; Humans; Lung; Male; Middle Aged; Mycobacterium Infections, Nontuberculous; Oxazines; Piperazines; Pyridones; Rifabutin; Tenofovir; Tomography, X-Ray Computed

Bloodstream infection (BSI) after allogeneic hematopoietic stem cell transplantation (HSCT) is a well-known complication during the pre-engraftment phase. Knowledge of trends in etiology and antibiotic susceptibility of BSI is important as the time to effective antibiotic treatment is closely associated with survival in bacteremic patients with septic shock.. BSI during the pre-engraftment phase was studied retrospectively in 521 patients undergoing HSCT at our center in 2001-2008. Incidence, risk factors, outcome, and microbiology findings were investigated and compared with BSI in a cohort transplanted during 1975-1996.. The incidence of at least 1 episode of BSI was 21%, the total attributable mortality of BSI was 3.3%, and crude mortality at day 120 after transplantation was 21%. The rate of gram-positive and gram-negative BSI was 80% and 13%, respectively. Gram-negative BSI was more frequent both in 2001-2004 and in 2005-2008 compared with 1986-1996 (P = 0.023 for 2001-2004, P = 0.001 for 2005-2008), with fluoroquinolone-resistant Escherichia coli as the predominant finding. BSI with viridans streptococci and E. coli occurred significantly earlier after HSCT than BSI with Enterococcus species, with median time of 4, 8, and 11 days, respectively (P < 0.01 both for viridians streptococci vs. Enterococcus species, and E. coli vs. Enterococcus species). Risk factors for BSI in multivariate analysis were transplantation from unrelated donor and cord blood as stem cell source, whereas peripheral blood as stem cell source was protective.. Despite low attributable mortality of BSI, crude mortality at day 120 after transplantation was 21%, indicating an association between BSI and other risk factors for death. The risk of gram-negative BSI increased over time in parallel with an increased rate of quinolone resistance. However, the incidence and attributable mortality of gram-negative BSI remained low. Thus, prophylaxis with ciprofloxacin is still deemed appropriate, but continued assessments of the risk and benefits of fluoroquinolone prophylaxis must be performed.

Topics: Adolescent; Adult; Aged; Amphotericin B; Anti-Infective Agents; Bacteremia; Candidiasis; Child; Child, Preschool; Ciprofloxacin; Cohort Studies; Enterococcus; Female; Fluconazole; Fungemia; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Infant; Male; Middle Aged; Multivariate Analysis; Neutropenia; Retrospective Studies; Risk Factors; Staphylococcal Infections; Streptococcal Infections; Time Factors; Transplantation, Homologous; Viridans Streptococci; Young Adult

Lichtheimia corymbifera (syn. Absidia corymbifera, Mycocladus corymbifer) is an ubiquitous cosmopolitan mold that can cause primary cutaneous and deep tissue infection in healthy individuals. We report a subcutaneous L. corymbifera infection in a 13-year-old immune-competent child, with a severe traumatic injury, with a successful outcome after early diagnosis and treatment with lipid amphotericin B, early debridement, and vacuum-assisted closure (VAC).

Topics: Absidia; Accidents, Traffic; Adolescent; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Bacteremia; Combined Modality Therapy; Compartment Syndromes; Debridement; Early Diagnosis; Fractures, Bone; Humans; Immunocompetence; Leg Bones; Male; Mucormycosis; Multiple Trauma; Negative-Pressure Wound Therapy; Opportunistic Infections; Surgical Wound Infection; Wound Infection

Reported here are the features of a Rhodotorula mucilaginosa outbreak that occurred in a neonatal intensive care unit. Over a period of 19 days, clinical and laboratory signs of sepsis appeared in four premature infants carrying indwelling vascular catheters. After bloodstream infection with R. mucilaginosa was ascertained, the patients underwent amphotericin B therapy and recovered completely. In a retrospective case-control study, the variables displaying a statistical difference between case and control-group neonates were birth weight, gestational age, duration of parenteral nutrition, duration of antibiotic therapy and prophylactic administration of fluconazole. To our knowledge, this is the first reported outbreak caused by yeasts of the Rhodotorula genus.

Topics: Amphotericin B; Antifungal Agents; Bacteremia; Case-Control Studies; Catheterization, Central Venous; Catheters, Indwelling; Disease Outbreaks; Female; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Intensive Care Units, Neonatal; Male; Mycoses; Rhodotorula

A 46-year-old previously healthy woman was diagnosed with acute lymphoblastic leukaemia. The induction phase was complicated by alpha-haemolytic streptococcal bacteremia which responded to antibacterial therapy. Subsequently, the patient developed pneumonie due to Chlamydiapneumoniae which responded to macrolides. Following this infection the patient developed recurrent fever and new pulmonary infiltrates were noted. Bronchoscopy was performed and treatment was administered with liposomal amphotericin B (L-AmB, AmBisome) for two days, but was complicated by acute renal failure. Aspergillus fumigatus was cultured from bronchoalveolar lavage fluid [corrected] L-AmB was discontinued and voriconazole and caspofungin were administered. Despite aggressive antifungal therapy the patient developed progressive invasive infection, with central nervous system involvement as well as lesions appearing in the kidneys and liver. The patient died one week following the diagnosis of aspergillosis.

Topics: Acute Kidney Injury; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Bacteremia; Caspofungin; Chlamydophila Infections; Chlamydophila pneumoniae; Doxorubicin; Drug Resistance, Multiple, Fungal; Drug Therapy, Combination; Echinocandins; Fatal Outcome; Female; Humans; Immunocompromised Host; Lipopeptides; Liposomes; Lung Diseases, Fungal; Medical Futility; Methotrexate; Middle Aged; Neuroaspergillosis; Peptides, Cyclic; Pneumonia, Bacterial; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Pyrimidines; Streptococcal Infections; Triazoles; Vincristine; Voriconazole

Amphotericin B is the primary antifungal agent used for candida sepsis in neonates. Breakthrough candidemia was not reported in neonates during either amphotericin B or liposomal amphotericin B (AmBisome) treatment. We describe a case of a premature infant with congenital cutaneous candida infection, who had two episodes of breakthrough infection, from Candida albicans and Candida parapsilosis, while he was treated with amphotericin B and AmBisome, respectively. We discuss the pathogenesis of breakthrough infections, and the relevance of antifungal resistance and sensitivities testing.

Topics: Amphotericin B; Antifungal Agents; Bacteremia; Candidiasis; Candidiasis, Cutaneous; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Male; Microbial Sensitivity Tests; Pregnancy

A 66-year-old woman with malignant lymphoma became neutropenic during chemotherapy and developed cryptococcemia. After amphotericin B had been commenced, she developed significant hypokalemia and polyuria, though her renal function remained stable. The laboratory findings showed no evidence of renal tubular acidosis. With vigorous water and potassium replacement, amphotericin B had been continued until the cumulative dose reached 2.5 g. After the cessation of amphotericin B, the hypokalemia and polyuria resolved promptly. Based on theses findings, she was diagnosed as nephrogenic diabetes insipidus with hypokalemia and without renal tubular acidosis due to amphotericin B. This complication is usually reversible, and vigorous water and potassium replacement may allow completion of treatment by amphotericin B, though careful monitoring of body water balance and renal function is of importance.

Topics: Aged; Amphotericin B; Antifungal Agents; Antigens, Fungal; Antimetabolites, Antineoplastic; Bacteremia; Cryptococcosis; Cryptococcus neoformans; Diabetes Insipidus, Nephrogenic; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Lymphoma; Mercaptopurine; Tomography, X-Ray Computed

A common complication of the intensive therapy that children with cancer receive is infection. The Oncology Unit of The Children's Hospital at Westmead maintains a comprehensive database of all admissions for suspected sepsis. From July 1994 to June 1999 broad-spectrum antibiotics were commenced in 2331 episodes. With early and aggressive use of empirical amphotericin B, 545 courses were given. Bacteraemia was documented in 701 episodes and invasive fungal disease in 73. Trends seen during the study included: (i) the proportion of febrile neutropenic patients receiving granulocyte colony stimulating factor increased from 40% to 60%; (ii) the mean neutrophil count at cessation of antibiotics fell from 0.97 to 0.63 x 10(9) cells/L for patients not receiving growth factors; (iii) the proportion of non-albicans Candida species infections increased. In addition, an outbreak of infection caused by Scedosporium sp. was documented; (iv) first-line empirical antibiotic combinations containing vancomycin fell from 20% to 7%; and (v) the ability to maintain or escalate anti-fungal therapy with reduced nephrotoxicity through use of lipid formulations of amphotericin was increasingly apparent in high-risk patients. During the study, infection was the primary cause of death in 11 non-bone marrow transplant (BMT) patients (five fungal, four viral, one bacterial infection and one sepsis syndrome) and five BMT patients (two bacterial and three viral). A prospective randomized study of toxicity due to amphotericin B given in either lipid emulsion or dextrose showed no significant difference, but both groups showed a lower incidence of amphotericin B intolerance in comparison with the adult series. The inability to reduce toxicity of amphotericin B by simple mixing with lipid emulsion has led to increasing use of commercially available lipid formulations of amphotericin B.

Topics: Amphotericin B; Antifungal Agents; Bacteremia; Child; Drug-Related Side Effects and Adverse Reactions; Humans; Mycoses; Neoplasms; Neutropenia; Randomized Controlled Trials as Topic

To determine the epidemiology of candidemia in our neonatal intensive care unit; to compare risk factors, clinical presentation, and outcomes for neonates infected with Candida albicans, Candida parapsilosis, and coagulase-negative staphylococcus (CoNS); and to suggest a rational approach to empiric antifungal therapy of neonates at risk for nosocomial infection.. Retrospective chart review of all neonatal intensive care unit patients with systemic candidiasis or CoNS infection between January 1, 1995 and July 31, 1998 at Duke University Medical Center.. Fifty-one patients were reviewed. Nine of 19 patients infected with C parapsilosis and 5 of 15 patients infected with C albicans died of fungemia. Seventeen neonates had >2 positive cultures for CoNS obtained within 96 hours and 1 died. There was no statistically significant difference in birth weight, gestational age, or age at diagnosis between patient groups; however, candidemic patients had a sevenfold higher mortality rate. Before diagnosis, candidemic patients had greater exposure to systemic steroids, antibiotics, and catecholamine infusions. Of the 51 patients, 32 received third-generation cephalosporins in the 2 weeks before diagnosis and 19 did not. Twenty-nine of the 32 who were treated with third-generation cephalosporins subsequently developed candidemia, while candidemia occurred in only 5 of 19 patients who were not treated with cephalosporins. At the time of diagnosis, candidemic patients were more likely to have required mechanical ventilation and were less likely to be tolerating enteral feeding. Multivariate clustered logistic regression analysis revealed that candidemic patients had more exposure to third-generation cephalosporins. Once the clinician was notified of a positive blood culture for Candida, patients infected with C parapsilosis retained their central catheters longer than patients infected with C albicans.. In this retrospective review, we were able to identify aspects of the clinical presentation and medication history that may be helpful in differentiating between candidemia and CoNS bacteremia. Those key features may be used by clinicians to initiate empiric amphotericin B therapy in premature neonates at risk for nosocomial infections. Prolonged use of third-generation cephalosporins was strongly associated with candidemia. There was no statistically significant difference in the morbidity and mortality between patients infected with C parapsilosis and those infected with C albicans. Observed delays in removal of the central venous catheter may have contributed to finding a mortality rate from C parapsilosis that was higher than was previously reported.

Topics: Amphotericin B; Analysis of Variance; Anti-Bacterial Agents; Antifungal Agents; Bacteremia; Candida; Candida albicans; Candidiasis; Catheterization, Central Venous; Cephalosporins; Cross Infection; Diagnosis, Differential; Fungemia; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Intensive Care Units, Neonatal; Logistic Models; Retrospective Studies; Risk Factors; Staphylococcal Infections

Cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and tumor necrosis factor-soluble receptor (TNF-sR), and adhesion molecules, e.g. vascular adhesion molecule-1 (VCAM-1) and E-selectin, play an important role in the pathogenesis of bacterial sepsis. Experimental data on cytokine expression during candidaemia are controversial. In this study, plasma concentrations of cytokines and adhesion molecules were compared between patients with sepsis due to Candida albicans and bacterial sepsis. Plasma levels of TNF-alpha, TNF-sR, IL-6, VCAM-1 and E-selectin, were determined in 20 patients with sepsis due to C. albicans, in 20 patients with bacterial sepsis, and in 20 controls on days 1, 7 and 14. On day 1, elevated plasma levels of TNF-alpha, TNF-sR and IL-6 were detected in both sepsis groups compared to controls. On day 1, VCAM-1 levels were higher, and E-selectin levels were lower in patients with Candida sepsis than in patients with bacterial sepsis (p < 0.05). At any time, VCAM-1 levels were significantly greater in patients with Candida sepsis than in patients with bacterial sepsis (p < 0.05). Non-survivors, regardless of the etiology of sepsis, had higher blood levels of IL-6, TNF-sR and E-selectin than survivors. The cytokines, TNF-alpha, IL-6 and TNF-sR, and the adhesion molecules, VCAM-1 and E-selectin, are involved in sepsis due to C. albicans as in bacterial sepsis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Bacteremia; Candidiasis; Cell Adhesion Molecules; Cytokines; Female; Fluconazole; Fungemia; Humans; Male; Middle Aged

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

Topics: Acyclovir; Amphotericin B; Bacteremia; Drug Therapy, Combination; Granulocyte Colony-Stimulating Factor; Hematologic Diseases; Herpesviridae Infections; Humans; Immunocompromised Host; Mycobacterium Infections; Mycoses

A patient with a history of alcohol abuse and pancreatitis presented with a pleural effusion resulting from a fistula between the pancreatic duct and left pleural space. Two weeks into her hospitalization, fever and persistent bloodstream infection with Erysipelothrix rhusiopathiae and Candida albicans developed. The patient had no history of exposure to animals. To our knowledge this is the first report of an E. rhusiopathiae infection presenting during hospitalization. This case suggests the possibility of a carrier state of infection and illustrates that a high index of suspicion is necessary for identification of unusual pathogens in hospitalized patients.

Topics: Adult; Amphotericin B; Bacteremia; Candidiasis; Carrier State; Cross Infection; Drug Resistance, Microbial; Erysipelothrix; Erysipelothrix Infections; Female; Humans; Microbial Sensitivity Tests; Pancreatic Fistula; Penicillin G; Pleural Effusion; Postoperative Complications

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

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