Luciano Zubaran Goldani

Pharmacokinetics of Intravenous Polymyxin B in Critically Ill Patients

BACKGROUND Although not much pharmacokinetic knowledge is available, polymyxin B is increasingly used for treatment of infections caused by gram-negative bacteria that are resistant to all other antibiotics. METHODS This study involved 8 patients who received intensive care after intravenous administration of a 60-min infusion of polymyxin B at currently recommended doses. Blood and urine samples were collected, and plasma protein binding of polymyxin B was determined. Concentrations of polymyxin B in plasma and urine samples were measured by a specific high-performance liquid chromatographic method. RESULTS Polymyxin B was well tolerated. The peak plasma concentrations at the end of the infusion varied from 2.38 to 13.9 mg/L. For 4 patients from whom it was possible to collect urine samples over a dosing interval, only 0.04%-0.86% of the dose was recovered in the urine in unchanged form. Plasma protein binding of polymyxin B was higher in samples from patients (range, 78.5%-92.4%) than in plasma samples from healthy human subjects (mean +/- standard deviation, 55.9% +/- 4.7%). Unbound plasma concentrations of polymyxin B were in the vicinity of or lower than the minimum inhibitory concentration of the pathogen. CONCLUSION To our knowledge, this is the first study to report plasma concentrations over time and urinary recovery of polymyxin B in critically ill patients after intravenous administration. Polymyxin B is eliminated mainly by nonrenal pathways, and the total body clearance appears to be relatively insensitive to renal function. Additional investigations are required to assess the appropriateness of currently recommended doses of this drug for the treatment of severe infections in critically ill persons.

Hemoplasma infection in HIV-positive patient, Brazil.

Hemotrophic mycoplasmas infect a variety of mammals. Although infection in humans is rarely reported, an association with an immunocompromised state has been suggested. We report a case of a Mycoplasma haemofelis–like infection in an HIV-positive patient co-infected with Bartonella henselae.

Epidemiology of Rhodotorula: An Emerging Pathogen

This is an updated paper focusing on the general epidemiological aspects of Rhodotorula in humans, animals, and the environment. Previously considered nonpathogenic, Rhodotorula species have emerged as opportunistic pathogens that have the ability to colonise and infect susceptible patients. Rhodotorula species are ubiquitous saprophytic yeasts that can be recovered from many environmental sources. Several authors describe the isolation of this fungus from different ecosystems, including sites with unfavourable conditions. Compared to R. mucilaginosa, R. glutinis and R. minuta are less frequently isolated from natural environments. Among the few references to the pathogenicity of Rhodotorula spp. in animals, there are several reports of an outbreak of skin infections in chickens and sea animals and lung infections and otitis in sheep and cattle. Most of the cases of infection due to Rhodotorula in humans were fungemia associated with central venous catheter (CVC) use. The most common underlying diseases included solid and haematologic malignancies in patients who were receiving corticosteroids and cytotoxic drugs, the presence of CVC, and the use of broad-spectrum antibiotics. Unlike fungemia, some of the other localised infections caused by Rhodotorula, including meningeal, skin, ocular, peritoneal, and prosthetic joint infections, are not necessarily linked to the use of CVCs or immunosuppression.

Update on the contribution of galactomannan for the diagnosis of invasive aspergillosis.

The diagnosis of invasive fungal infections (IFI) remains a challenge, particularly for diseases caused by filamentous fungi such as Aspergillus species. Unfortunately, many patients affected by these conditions are not identified before autopsy. Therefore, there is a need for new diagnostic methods for IFI. Galactomannan is a soluble antigen released during hyphal growth in tissues. A commercially available sandwich ELISA assay that detects galactomannan has been used in Europe for many years and is now approved for use in the USA. The test has an excellent negative predictive value in the detection of invasive aspergillosis (IA) in high-risk patients. In addition, it is more sensitive than culture and allows IA to be diagnosed before clinical manifestations occur. However, false-negative and false-positive results in certain populations are the main limitations to its use. The purpose of this review is to summarize the current knowledge about galactomannan testing in patients at risk for IA.

An Open-Label Comparative Pilot Study of Oral Voriconazole and Itraconazole for Long-Term Treatment of Paracoccidioidomycosis

BACKGROUND In previous studies, itraconazole was revealed to be an effective therapy and was considered to be the gold standard treatment for mild-to-moderate acute and chronic clinical forms of paracoccidioidomycosis. A pilot study was conducted to investigate the efficacy, safety, and tolerability of voriconazole for the long-term treatment of acute or chronic paracoccidioidomycosis, with itraconazole as the control treatment. METHODS A randomized, open-label study was conducted at 3 Brazilian tertiary care hospitals. Patients were randomized (at a 2 : 1 ratio) to receive oral therapy with voriconazole or itraconazole for 6 months. Patients receiving >or=1 dose of study drug were evaluated for safety; patients with confirmed paracoccidioidomycosis who completed >or=6 months of therapy (treatment-evaluable patients) were evaluated for treatment efficacy. Satisfactory global response was assessed at the end of treatment. RESULTS Fifty-three patients were evaluated for treatment safety (35 received voriconazole, and 18 received itraconazole). Both drugs were well tolerated. The most common treatment-related adverse events in the voriconazole group included abnormal vision, chromatopsia, rash, and headache; the most common treatment-related adverse events in the itraconazole group included bradycardia, diarrhea, and headache. Liver function test values were slightly higher in patients receiving voriconazole than in those receiving itraconazole; 2 patients in the voriconazole group were withdrawn from treatment because of increased liver function test values. In the intent-to-treat populations, the satisfactory response rate (i.e., complete or partial global response) was 88.6% among the voriconazole group and 94.4% among the itraconazole group. The response rate among treatment-evaluable patients was 100% for both treatment groups; no relapses were observed after 8 weeks of follow-up. CONCLUSIONS This is, to our knowledge, the first study to demonstrate that voriconazole is as well tolerated and effective as itraconazole for the long-term treatment of paracoccidioidomycosis.

Epidemiology and Outcome of Rhodotorula Fungemia in a Tertiary Care Hospital

We reviewed demographic data, risk factors, treatment, and outcomes associated with Rhodotorula fungemia in a tertiary care hospital during 2002-2005. Rhodotorula species caused fungemic episodes in 7 patients during the 4-year period that we studied. The most common predisposing factors were patients with hematological and solid malignancy receiving corticosteroids and cytotoxic drugs, the presence of central venous catheters, and the use of broad-spectrum antibiotics. Because of Rhodotorula speciess intrinsic resistance to triazole and echinocandin antifungal agents, patients receiving fluconazole and caspofungin might be susceptible to the development of breakthrough Rhodotorula fungemia.

Reappraisal of Pseudomonas aeruginosa hospital-acquired pneumonia mortality in the era of metallo-β-lactamase-mediated multidrug resistance: a prospective observational study

IntroductionHospital-acquired pneumonia (HAP) due to Pseudomonas aeruginosa is associated with high mortality rates. The metallo-β-lactamases (MBLs) are emerging enzymes that hydrolyze virtually all β-lactams. We aimed to assess P. aeruginosa HAP mortality in a setting of high-rate MBL productionMethodsA prospective cohort study was performed at two tertiary-care teaching hospitals. A logistic regression model was constructed to identify risk factors for 30-day mortality.ResultsOne-hundred and fifty patients with P. aeruginosa HAP were evaluated. The 30-day mortality was 37.3% (56 of 150): 57.1% (24 of 42) and 29.6% (32 of 108) for patients with HAP by MBL-producing P. aeruginosa and by non-MBL-producing P. aeruginosa, respectively (relative risk, 1.93; 95% confidence interval (CI), 1.30–2.85). The logistic regression model identified a higher Charlson comorbidity score (odds ratio, 1.21; 95% CI, 1.04–1.41), presentation with severe sepsis or septic shock (odds ratio, 3.17; 95% CI, 1.30–7.72), ventilator-associated pneumonia (odds ratio, 2.92; 95% CI, 1.18–7.21), and appropriate therapy (odds ratio, 0.24; 95% CI, 0.10–0.61) as independent factors for 30-day mortality. MBL production was not statistically significant in the final model.ConclusionMBL-producing P. aeruginosa HAP resulted in higher mortality rates, particularly in patients with ventilator-associated pneumonia, most probably related to the less frequent institution of appropriate antimicrobial therapy. Therapeutic approaches should be reviewed at institutions with a high prevalence of MBL.

Prevalence, susceptibility profile for fluconazole and risk factors for candidemia in a tertiary care hospital in southern Brazil

Bloodstream infections caused by yeast, Candida spp, are quite important clinically and epidemiologically due to a high mortality rate and an increasing number of non-albicans species with a more resistant (differentiated susceptibility) profile. We examined species prevalence and susceptibility profile for fluconazole and the risk for nosocomial infections by Candida spp at the Hospital de Clínicas de Porto Alegre, a general tertiary care hospital in southern Brazilian, through a retrospective study, beginning with positive cultures of hospitalized patients. The distribution by species in 131 documented episodes was as follows: Candida albicans (45%), C. parapsilosis (24.4%), C. tropicalis (15.3%), C. glabrata (6.9%), C. krusei (4.6%) and 3.8% other species (C. pelicullosa, C. guilliermondii, C. lusitaniae and C. kefyr). The vast majority of samples (121- 92.4%) were susceptible to fluconazole; the resistant or dose-dependent sensitive samples included only C. krusei and C. glabrata. Blood diseases (leukemia, lymphoma), or neoplasias (solid tumors), were found in 35.0% of the candidemia episodes. We noted the previous use of antibiotics in 128 (97.7%) patients, with 79.7% using three or more antibiotics before the candidemia episode. Other risk factors included a central venous catheter in 94 (71.8%) and abdominal surgery in 32 (24.4%) patients. The overall mortality rate was 51.9%, which varied according to the underlying disease. We found that C. albicans was the most prevalent species, although the non-albicans species predominated. However, in vitro resistance to fluconazole was detected only among the species (C. glabrata and C. krusei) that tend to be resistant to the azolic compounds. Previous use of antibiotic and the use of a central venous catheter were the main risk factors among patients with candidemia.

Mucocutaneous manifestations of disseminated histoplasmosis in patients with acquired immunodeficiency syndrome: particular aspects in a Latin‐American population

Summary Background.  Mucocutaneous lesions in human immunodeficiency virus (HIV)‐infected patients with disseminated histoplasmosis have a wide spectrum of clinical manifestations, making its diagnosis difficult. Studies have been restricted to case reports and series with small numbers of patients not specifically focusing on the dermatological aspects of histoplasmosis.

Microbiology of choledochal bile in patients with choledocholithiasis admitted to a tertiary hospital

Aim: The present study was designed to investigate the microbiology of choledochal bile of patients with cholangitis and choledocholithiasis.