Antimicrobial stewardship: The influence of behavioral nudging on renal-function-based appropriateness of dosing.

Failure to adjust doses may contribute to adverse events. We evaluated the effectiveness of providing the estimated glomerular filtration rate on appropriateness of dosing for antimicrobials. The approach increased appropriateness of dosing from 33.9% to 41.4% (P < .001). Nudging prescription behavior can boost strategies for adequate antimicrobial prescription.

Predicting the occurrence of surgical site infections using text mining and machine learning.

In this study we propose the use of text mining and machine learning methods to predict and detect Surgical Site Infections (SSIs) using textual descriptions of surgeries and post-operative patients' records, mined from the database of a high complexity University hospital. SSIs are among the most common adverse events experienced by hospitalized patients; preventing such events is fundamental to ensure patients' safety. Knowledge on SSI occurrence rates may also be useful in preventing future episodes. We analyzed 15,479 surgery descriptions and post-operative records testing different preprocessing strategies and the following machine learning algorithms: Linear SVC, Logistic Regression, Multinomial Naive Bayes, Nearest Centroid, Random Forest, Stochastic Gradient Descent, and Support Vector Classification (SVC). For prediction purposes, the best result was obtained using the Stochastic Gradient Descent method (79.7% ROC-AUC); for detection, Logistic Regression yielded the best performance (80.6% ROC-AUC).

Antimicrobial stewardship through telemedicine and its impact on multi-drug resistance.

INTRODUCTION: Telemedicine technologies are increasingly being incorporated into infectious disease practice. We aimed to demonstrate the impact of antimicrobial stewardship through telemedicine on bacterial resistance rates. METHODS: We conducted a quasi-experimental study in a 220-bed hospital in southern Brazil. An antimicrobial stewardship program incorporating the use of telemedicine was implemented. Resistance and antimicrobial consumption rates were determined and analysed using a segmented regression model. RESULTS: After the intervention, the rate of appropriate antimicrobial prescription increased from 51.4% at baseline to 81.4%. Significant reductions in the consumption of fluoroquinolones (level change, ß = -0.80; P < 0.01; trend change, ß = -0.01; P = 0.98), first-generation cephalosporins (level change, ß = -0.91; P < 0.01; trend change, ß = +0.01; P = 0.96), vancomycin (level change, ß = -0.47; P = 0.04; trend change, ß = +0.17; P = 0.66) and polymyxins (level change, ß = -0.15; P = 0.56; trend change, ß = -1.75; P < 0.01) were identified. There was an increase in the consumption of amoxicillin + clavulanate (level change, ß = +0.84; P < 0.01; trend change, ß = +0.14; P = 0.41) and cefuroxime (level change, ß = +0.21; P = 0.17; trend change, ß = +0.66; P = 0.02). A significant decrease in the rate of carbapenem-resistant Acinetobacter spp. isolation (level change, ß = +0.66; P = 0.01; trend change, ß = -1.26; P < 0.01) was observed. CONCLUSIONS: Telemedicine, which provides a tool for decision support and immediate access to experienced specialists, can promote better antibiotic selection and reductions in bacterial resistance.

Association between Accessory Gene Regulator Polymorphism and Mortality among Critically Ill Patients Receiving Vancomycin for Nosocomial MRSA Bacteremia: A Cohort Study.

Background. Polymorphism of the accessory gene regulator group II (agr) in methicillin-resistant Staphylococcus aureus (MRSA) is predictive of vancomycin failure therapy. Nevertheless, the impact of group II agr expression on mortality of patients with severe MRSA infections is not well established. Objective. The goal of our study was to evaluate the association between agr polymorphism and all-cause in-hospital mortality among critically ill patients receiving vancomycin for nosocomial MRSA bacteremia. Methods. All patients with documented bacteremia by MRSA requiring treatment in the ICU between May 2009 and November 2011 were included in the study. Cox proportional hazards regression was performed to evaluate whether agr polymorphism was associated with all-cause in-hospital mortality. Covariates included age, APACHE II score, initial C-reactive protein plasma levels, initial serum creatinine levels, vancomycin minimum inhibitory concentration, vancomycin serum levels, and time to effective antibiotic administration. Results. The prevalence of group I and group II agr expression was 52.4% and 47.6%, respectively. Bacteremia by MRSA group III or group IV agr was not documented in our patients. The mean APACHE II of the study population was 24.3 (standard deviation 8.5). The overall cohort mortality was 66.6% (14 patients). After multivariate analysis, initial plasma C-reactive protein levels (P = 0.01), initial serum creatinine levels (P = 0.008), and expression of group II agr (P = 0.006) were positively associated with all-cause in-hospital mortality. Patients with bacteremia by MRSA with group II agr expression had their risk of death increased by 12.6 times when compared with those with bacteremia by MRSA with group I agr expression. Conclusion. Group II agr polymorphism is associated with an increase in mortality in critically ill patients with bacteremia by MRSA treated with vancomycin.

Comparison of anti-anaerobic antimicrobial strategies in cancer patients with febrile neutropenia and gastrointestinal symptoms.

BACKGROUND: The current study sought to compare 28-day mortality rates in cancer patients with febrile neutropenia (FN) and gastrointestinal (GI) symptoms who underwent monotherapy using an antibiotic with antipseudomonal and anti-anaerobic activity (piperacillin-tazobactam or a carbapenem) and a group treated with a combination of cefepime-metronidazole. FINDINGS: We performed a prospective cohort study in a single tertiary hospital from October 2009 to August 2011. All consecutive adult cancer patients admitted with FN secondary to intensive chemotherapy and GI symptoms (abdominal pain, diarrhea or perianal pain) were evaluated. Kaplan-Meier curves were used for calculating time-dependent occurrence of death. In total, 37 patients with FN and GI symptoms were evaluated (15 in monotherapy arm and 22 in the combination therapy arm). Treatment with combination cefepime and metronidazole resulted in a lower 28-day mortality rate compared with piperacillin-tazobactam or carbapenem monotherapy (0% versus 40%; log-rank P=0.002). CONCLUSIONS: Results of the present study suggest a significant reduction in mortality in cancer patients with FN and GI symptoms treated with combination cefepime-metronidazole therapy compared with monotherapy using agents with antipseudomonal and anti-anaerobic activity. Further randomized trials are warranted to confirm the superior results using combination therapy in patients with FN and GI symptoms.

Association between adherence to an antimicrobial stewardship program and mortality among hospitalised cancer patients with febrile neutropaenia: a prospective cohort study.

BACKGROUND: Initial management of chemotherapy-induced febrile neutropaenia (FN) comprises empirical therapy with a broad-spectrum antimicrobial. Currently, there is sufficient evidence to indicate which antibiotic regimen should be administered initially. However, no randomized trial has evaluated whether adherence to an antimicrobial stewardship program (ASP) results in lower rates of mortality in this setting. The present study sought to assess the association between adherence to an ASP and mortality among hospitalised cancer patients with FN. METHODS: We conducted a prospective cohort study in a single tertiary hospital from October 2009 to August 2011. All adult patients who were admitted to the haematology ward with cancer and FN were followed up for 28 days. ASP adherence to the initial antimicrobial prescription was determined. The mortality rates of patients who were treated with antibiotics according to the ASP protocol were compared with those of patients treated with other antibiotic regimens. The multivariate Cox proportional hazards model and propensity score were used to estimate 28-day mortality risk. RESULTS: A total of 307 FN episodes in 169 subjects were evaluated. The rate of adherence to the ASP was 53%. In a Cox regression analysis, adjusted for propensity scores and other potential confounding factors, ASP adherence was independently associated with lower mortality (hazard ratio, 0.36; 95% confidence interval, 0.14-0.92). CONCLUSIONS: Antimicrobial selection is important for the initial management of patients with FN, and adherence to the ASP, which calls for the rational use of antibiotics, was associated with lower mortality rates in this setting.

Vancomycin-resistant Enterococcus faecium Bacteremia in a tertiary care hospital: epidemiology, antimicrobial susceptibility, and outcome.

Vancomycin-resistant Enterococcus faecium (VREF) has emerged as a relevant multidrug-resistant pathogen and potentially lethal etiology of health care associated infections worldwide. The objective of this retrospective cohort study was to assess factors associated with mortality in patients with VREF bacteremia in a major tertiary referral hospital in Southern Brazil. All documented cases of bacteremia identified between May 2010 and July 2012 were evaluated. Cox regression was performed to determine whether the characteristics related to the host or antimicrobial treatment were associated with the all-cause 30-day mortality. In total, 35 patients with documented VREF bacteremia were identified during the study period. The median APACHE-II score of the study population was 26 (interquartile range: 10). The overall 30-day mortality was 65.7%. All VREF isolates were sensitive to linezolid, daptomycin, and quinupristin-dalfopristin. Linezolid was the only antimicrobial agent with in vitro activity against VREF that was administered to the cohort. After multivariate analysis, linezolid treatment (HR, 0.08; 95% CI, 0.02-0.27) and presence of acute kidney injury at the onset of bacteremia (HR, 4.01; 95% CI, 1.62-9.94) were independently associated with mortality. Presentation with acute kidney injury and lack of treatment with an effective antibiotic poses risk for mortality in patients with VREF bacteremia.

Mortality related to coagulase-negative staphylococcal bacteremia in febrile neutropenia: A cohort study.

BACKGROUND: Coagulase-negative staphylococci (CoNS) are currently the most common isolates recovered from the blood of patients with cancer and febrile neutropenia (FN). OBJECTIVES: To assess the mortality associated with bloodstream infections (BSIs) caused by CoNS in cancer patients with FN. METHODS: A prospective cohort study was conducted in a single tertiary hospital from October 2009 to August 2011. Follow-ups were performed on all of the adult patients who were admitted to the hematology ward with cancer and FN. Bacteremia caused by CoNS was defined as two positive results of two independent cultures. Twenty-eight days after the onset of FN, the mortality rates of the patients with BSIs caused by CoNS were compared with those of patients with BSIs caused by other pathogens. RESULTS: A total of 169 subjects were evaluated. During the study period, 78 patients with BSIs were documented. Twenty-three BSIs (29.4%) were a result of CoNS. CoNS-induced bacteremia resulted in lower 28-day mortality compared with bacteremia caused by other pathogens (4.3% versus 32.7%; log-rank P=0.009). In a Cox proportional hazards regression analysis, BSIs caused by CoNS were independently associated with lower mortality (HR 0.09 [95% CI 0.01 to 0.74]). CONCLUSIONS: In adult patients with cancer and FN, BSIs caused by CoNS were associated with lower mortality compared with BSIs caused by other pathogens.

HISTORIQUE: Les staphylocoques à coagulase négative (SCoN) sont les isolats les plus prélevés dans le sang des patients atteints d'un cancer et d'une neutropénie fébrile (NF). OBJECTIFS: Évaluer la mortalité associée aux infections sanguines (IS) causées par les SCoN chez des patients atteints du cancer ayant une NF. MÉTHODOLOGIE: Les chercheurs ont mené une étude prospective de cohorte dans un seul hôpital de soins tertiaires entre octobre 2009 et août 2011. Ils ont assuré le suivi de tous les patients adultes atteints d'un cancer et d'une neutropénie fébrile qui avaient été hospitalisés à l'unité d'hématologie. Les bactériémies causées par les SCoN étaient définies comme deux résultats positifs dans deux cultures indépendantes. Vingt-huit jours après l'apparition de la NF, le taux de mortalité des patients atteints d'une IS causée par des SCoN était comparé à celui des patients ayant une IS causée par d'autres pathogènes. RÉSULTATS: Au total, les chercheurs ont évalué 169 sujets. Pendant la période de l'étude, ils ont répertorié 78 patients ayant une IS. Vingttrois IS (29,4 %) étaient causées par un SCoN. La bactériémie induite par un SCoN était responsable d'un taux de mortalité plus faible au bout de 28 jours que celle causée par d'autres pathogènes (4,3 % par rapport à 32,7 %; test de Mantel Haenzel P=0,009). Dans une analyse de régression des hasards proportionnels de Cox, les IS causées par un SCoN étaient associées indépendamment à un taux de mortalité plus faible (rapport de risque 0,09 [95 % IC 0,01 à 0,74]). CONCLUSIONS: Chez des patients adultes atteints du cancer et de NF, les IS causées par un SCoN s'associaient à un taux de mortalité moins élevé que celles causées par d'autres pathogènes.

Risk factors for multidrug-resistant bacteremia in hospitalized cancer patients with febrile neutropenia: a cohort study.

We conducted a prospective cohort study in a single tertiary hospital with the aim of assessing predictors of multidrug-resistant bacteremia in 307 cases of febrile neutropenia in adult patients with cancer. On multivariate analysis using stepwise logistic regression, age (P = .009), duration of neutropenia (P = .022), and presence of an indwelling central venous catheter (P = .022) were associated with bloodstream infection by multidrug-resistant bacteria.

Epithelium and stroma from nasal polyp mucosa exhibits inverse expression of TGF-ß1 as compared with healthy nasal mucosa.

OBJECTIVE: To evaluate TGF-ß1 expression in polypoid mucosa (epithelium and stroma) of patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). METHODS: Cross-sectional study with two groups: 17 patients with nasal polyposis and 11 controls. Polyps and normal nasal mucosa were processed by immunohistochemical methods for TGF-ß1 visualization. Then, the percentage of TGF-ß1 expression in stroma and epithelium was objectively quantified using UT Morph software. RESULTS: A lower percentage of positive expression was found in the epithelium of CRSwNP patients (32.44%) versus normal controls (55.91%) (p < 0.05), and a higher percentage of positive expression in the stroma of CRSwNP patients (23.24%) versus controls (5.88%) (p < 0.05). CONCLUSION: The lower percentage of TGF-ß1 expression in the nasal epithelium of CRSwNP patients may have an impact on epithelium-directed topical treatments employed in this patient population.

Continuous infusion of amphotericin B deoxycholate: an innovative, low-cost strategy in antifungal treatment.

The combination of amphotericin B and sodium deoxycholate is the formulation most used in clinical practice. The development of new agents such as amphotericin with lipid formulations, caspofungin, voriconazole and other azolic derivatives, promoted alternatives to amphotericin B deoxycholate. However, because of the high cost of these new drugs, their use is difficult in a scenario of limited resources. A few strategies have been devised to make the use of amphotericin B deoxycholate less toxic. In this review, we seek to describe the accumulated knowledge about this molecule, with focus on its use in continuous infusion, which appears to be an alternative to reduce toxicity, while maintaining its clinical efficacy.

Candida tropicalis as an emerging pathogen in Candida meningitis: case report and review

Candida species are an uncommon cause of meninigitis. Given the rarity of this infection, the epidemiology, prognosis, and optimal therapy for Candida meningitis are poorly defined. The authors report on a paraplegic patient due to spinal cord injury who developed C. tropicalis meningitis. In addition, we review and discuss other reported cases of C. tropicalis meningitis in the medical literature.

Candida tropicalis as an emerging pathogen in Candida meningitis: case report and review.

Candida species are an uncommon cause of meninigitis. Given the rarity of this infection, the epidemiology, prognosis, and optimal therapy for Candida meningitis are poorly defined. The authors report on a paraplegic patient due to spinal cord injury who developed C. tropicalis meningitis. In addition, we review and discuss other reported cases of C. tropicalis meningitis in the medical literature.

Two specific strains of Histoplasma capsulatum causing mucocutaneous manifestations of histoplasmosis: preliminary analysis of a frequent manifestation of histoplasmosis in southern Brazil.

OBJECTIVES: Skin lesions, uncommon in US cases (<10%), occur in 38-85% of cases reported from Latin America. Although these differences may reflect reporting bias, delayed diagnosis, or differences in host immune response among different ethnic groups, they also could result from genetic differences changing the pathobiology of the organism. It is possible that genetic differences among strains of H. capsulatum may influence the pathogenesis and clinical manifestations of histoplasmosis. METHODS: We examined the clinical features of patients with mucocutaneous manifestations of histoplasmosis and performed genetic analysis based on nucleotide sequence variations in the internal transcribed spacer regions of rRNA genes of H. capsulatum isolates of patients. Two pairs of PCR primers were designed to develop and amplify the ITS regions of H. capsulatum, 5'-TACCCGGCCACCCTTGTCTA-3' and 5'-AGCGGGTGGCAAAGCCC-3'. These primers were based on the ITS sequence of Ajellomyces capsulatus, the ascomycetous teleomorph form of H. capsulatum, deposited in the GenBank (accession number U18363). Eight patients attending a tertiary-care hospital in southern Brazil were enrolled into the study. All case patients had skin cultures growing H. capsulatum at the mycology laboratory. RESULTS: Six of eight (75%) patients were HIV-positive and presented involvement of multiples organs by H. capsulatum. Two HIV-negative patients did not present evidence of involvement of other organs besides mucosa and skin. ITS sequencing of a DNA H. capsulatum fragment of 485-bp from isolates of 8 patients revealed two distinct strains. The 2 distinct fragments (Hc1, Hc2) differed from each other at 7 positions in the ITS regions. They were identical to strains of H. capsulatum isolated in patients from Colombia and Argentina, but different from strains isolated in US. Hc1 and Hc2 were isolated in 5 patients and 3 patients, respectively, with mucocutaneous manifestations of histoplasmosis. Both Hc1 and Hc2 strains were isolated in HIV-infected and non-HIV-infected patients. CONCLUSIONS: Mucocutaneous manifestations of histoplasmosis, which are frequently seen in Brazilian patients were caused by 2 specific strains in our institution. Those strains have been isolated in patients with these particular clinical features of histoplasmosis in Latin America. Our study suggests that unique pathogenic characteristics among the Latin American species of H. capsulatum might explain its increased dermatotropism.

The effect of epibionts on the susceptibility of the red seaweed Cryptonemia seminervis to herbivory and fouling.

Epibiosis or fouling on living organisms can have direct and indirect detrimental effects, in particular on photosynthetic organisms such as seaweeds. It thus seems reasonable to hypothesize that macroalgae have been selected for the presence or induction of antifouling (AF) defences. The red seaweed Cryptonemia seminervis is usually found in nature with an elevated cover of epibionts. To assess the effect of epibiosis on the susceptibility of this seaweed to herbivory and fouling, the abundance of fouling was evaluated and compared to herbivore consumption (by amphipods and sea urchins) of fouled (bryozoan and sponge) and non-fouled C. seminervis. Attachment of the mussel Perna perna to surfaces treated with extracts from seaweeds with and without epibionts was also assessed. Epibiosis corresponded to ca. 51% of the blade surface of C. seminervis, sometimes covering as much as 90% and up to 51% of the thallus weight, encompassing mainly the bryozoan Membranipora membranacea and an unidentified sponge. Algae colonized by M. membranacea were preferred compared to algae devoid of epibionts, a 'shared doom' effect, either by the amphipod Elasmopus brasiliensis or by the urchin Lytechinus variegatus (p < 0.01). Sponge epibiosis also increased consumption by both herbivores (p < 0.001), suggesting that epibionts may act as lures to herbivores, attracting consumers that otherwise would not feed significantly on the seaweed. Foods containing extracts from fouled C. seminervis were preferred by urchins over the alga devoid of epibionts. However, extracts from fouled alga inhibited mussel attachment when compared to epibiont-free alga. Differences might be a direct detrimental effect of the presence of epibionts. On the other hand, epibiosis may induce the production of AF defences in C. seminervis.

Comparative radiological features of disseminated disease due to Mycobacterium tuberculosis vs non-tuberculosis mycobacteria among AIDS patients in Brazil.

BACKGROUND: Disseminated mycobacterial disease is an important cause of morbidity and mortality in patients with HIV-infection. Nonspecific clinical presentation makes the diagnosis difficult and sometimes neglected. METHODS: We conducted a retrospective cohort study to compare the presentation of disseminated Mycobacterial tuberculosis (MTB) and non-tuberculous Mycobacterial (NTM) disease in HIV-positive patients from 1996 to 2006 in Brazil. RESULTS: Tuberculosis (TB) was diagnosed in 65 patients (67.7%) and NTM in 31 (32.3%) patients. Patients with NTM had lower CD4 T cells counts (median 13.0 cells/mm3 versus 42.0 cells/mm3, P = 0.002). Patients with tuberculosis had significantly more positive acid-fast smears (48.0% vs 13.6%, P = 0.01). On chest X-ray, miliary infiltrate was only seen in patients with MTB (28.1% vs. 0.0%, P = 0.01). Pleural effusion was more common in patients with MTB (45.6% vs. 13.0%, P = 0.01). Abdominal adenopathy (73.1% vs. 33.3%, P = 0.003) and splenic hypoechoic nodules (38.5% vs. 0.0%, P = 0.002) were more common in patients with TB. CONCLUSION: Miliary pulmonary pattern on X-ray, pleural effusion, abdominal adenopathy, and splenic hypoechoic nodules were imaging findings associated with the diagnosis of tuberculosis in HIV-infected patients. Recognition of these imaging features will help to distinguish TB from NTM in AIDS patients with fever of unknown origin due to disseminated mycobacterial disease.

Microarray cDNA to identify inflammatory genes in nasal polyposis.

BACKGROUND: The objective of this study was to investigate the spectrum of inflammatory gene expression in patients with nasal polyposis. METHODS: The cDNA microarray technique was used to identify gene expression in tissue samples from nasal polyps and adjacent inflammatory nasal mucosa of 21 patients with nonallergic nasal polyposis. To validate the microarray analysis, we compared the expression of five genes by reverse transcription-polymerase chain reaction (RT-PCR): tumor necrosis factor, IL-5, IL-9, fibroblast growth factor, and transforming growth factor (TGF)-beta1. RESULTS: We tested 96 different inflammatory genes in our samples. Thirty-six genes exhibited differences in expression between the two tissue types. In all 36 genes the level of expression was greater in the inflammatory mucosa than the polyps. The RT-PCR confirmed the cDNA results. CONCLUSION: We believe that the high expression of TGF-beta1 in inflammatory mucosa compared with the low expression in polyps may reflect an important role in the inhibitory mechanisms of nasal polyposis.

Microscopy and polymerase chain reaction detection of Leishmania chagasi in the pleural and ascitic fluid of a patient with AIDS: Case report and review of diagnosis and therapy of visceral leishmaniasis.

Atypical visceral leishmaniasis is increasingly reported in immunocompromised patients, including patients with AIDS. A case of visceral leishmaniasis in an HIV-infected Brazilian patient with pulmonary and peritoneal involvement is reported. Histological evaluation of pleural fluid and ascites aspirate revealed macrophages with intracellular Leishmania. Polymerase chain reaction analysis was positive for Leishmania in the pleural and ascitic fluid with use of primers specific for Leishmania chagasi. In addition to classical methods for diagnosing leishmaniasis, such as microscopy and culture, polymerase chain reaction detection and identification of Leishmania species in pleural effusions and ascites are important diagnostic tools that should be considered by clinicians evaluating HIV-infected patients from endemic areas of visceral leishmaniasis. The authors review the clinical manifestations, diagnostic and therapeutic aspects of visceral leishmaniasis in immunocompetent and HIV-infected patients.