Pharmacokinetic/pharmacodynamic target attainment of intravenous β-lactam regimens against Gram-negative bacteria isolated in a Brazilian teaching hospital

ABSTRACTINTRODUCTION: Monte Carlo simulations have been used for selecting optimal antibiotic regimens for treatment of bacterial infections. The aim of this study was to assess the pharmacokinetic and pharmacodynamic target attainment of intravenous β-lactam regimens commonly used to treat bloodstream infections (BSIs) caused by Gram-negative rod-shaped organisms in a Brazilian teaching hospital.METHODS: In total, 5,000 patients were included in the Monte Carlo simulations of distinct antimicrobial regimens to estimate the likelihood of achieving free drug concentrations above the minimum inhibitory concentration (MIC; fT > MIC) for the requisite periods to clear distinct target organisms. Microbiological data were obtained from blood culture isolates harvested in our hospital from 2008 to 2010.RESULTS: In total, 614 bacterial isolates, including Escherichia coli, Enterobacterspp., Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, were analyzed Piperacillin/tazobactam failed to achieve a cumulative fraction of response (CFR) > 90% for any of the isolates. While standard dosing (short infusion) of β-lactams achieved target attainment for BSIs caused by E. coliand Enterobacterspp., pharmacodynamic target attainment against K. pneumoniaeisolates was only achieved with ceftazidime and meropenem (prolonged infusion). Lastly, only prolonged infusion of high-dose meropenem approached an ideal CFR against P. aeruginosa; however, no antimicrobial regimen achieved an ideal CFR against A. baumannii.CONCLUSIONS:These data reinforce the use of prolonged infusions of high-dose β-lactam antimicrobials as a reasonable strategy for the treatment of BSIs caused by multidrug resistant Gram-negative bacteria in Brazil.

Occurrence and sensitivity profile of extended spectrum beta-lactamase-producing Enterobacteriaceae at a tertiary hospital in Southern Brazil

Abstract: INTRODUCTION: Nosocomial infections are closely associated with antimicrobial drug resistance. One of the most important mechanisms of resistance to β-lactam antibiotics is the production of extended spectrum β-lactamases (ESBLs). The objective of the present study was to evaluate the prevalence and antimicrobial susceptibility profile of ESBL-producing strains and to assess the evolution of antimicrobial drug resistance between 2007 and 2013 at the Hospital São Vicente de Paulo, Passo Fundo, State of Rio Grande do Sul, Brazil. METHODS: We conducted a descriptive, observational, cross-sectional study. Bacterial culture was performed from January to December 2013. The antimicrobial susceptibility profile of these cultures was determined using the disk diffusion method. Phenotypic screening for ESBL production was performed using the disk approximation method. RESULTS : We analyzed a total of 19,112 cultures, 11.5% of which were positive for Enterobacteriaceae. Of these, 30.3% of the isolates were positive for ESBL production, and the most prevalent species was Klebsiella sp. (37.5%). Over 95% of these isolates showed reduced susceptibility to all cephalosporins, aztreonam, and amoxicillin/clavulanic acid. The isolates also showed high sensitivity to the following antimicrobials: amikacin, meropenem, and piperacillin/tazobactam. Overall, the resistance rates among ESBL-producing Enterobacteriaceae decreased from 2007 to 2013. CONCLUSIONS : In our hospital, the increased sensitivity to certain antimicrobial agents seems to be directly related to the implementation of improvements in the methods to prevent and control nosocomial infections in addition to the natural development of other resistance mechanisms.

Severe dengue in the early postoperative period after kidney transplantation: two case reports from Hospital Geral de Fortaleza

Abstract: Dengue is an arbovirosis that ranges from an asymptomatic presentation to a more severe disease, which is characterized by a vascular leakage syndrome where abdominal pain is a major symptom. Transplant recipients are immunosuppressed and are less likely to develop a severe form of the disease because of a reduction in immune-mediated responses that trigger plasma extravasation events. Herein, we report two cases of severe dengue in the early postoperative period of two kidney transplant recipients. Considering the severity of the cases, we emphasize the importance of dengue screening immediately before transplantation in areas endemic for the disease.

Clinical, demographic, and epidemiologic characteristics of hepatitis B virus-infected patients at a tertiary public hospital in Presidente Prudente, State of São Paulo, Brazil

Abstract: INTRODUCTION: Few studies have addressed the primary characteristics of patients infected with hepatitis B virus (HBV) in the general population, especially those living in small- and medium-sized cities in Brazil. We aimed to determine the clinical, demographic, and epidemiologic characteristics of patients diagnosed with HBV who were followed up at an infectious diseases clinic of a public hospital in State of São Paulo, Brazil. METHODS: Medical records of patients aged >18 years and diagnosed with HBV infection between January 2000 and December 2013 were reviewed. RESULTS: Seventy-five patients were enrolled with male-female main infection-associated risk factors; 9 (12%) were co-infected with human immunodeficiency virus (HIV), 5 (6.7%) with hepatitis C virus (HCV), and 3 (4%) were co-infected with both HIV and HCV. Antiviral HBV therapy was applied in 21 (28%) patients and tenofovir monotherapy was the most prescribed medication. After approximately 2 years of antiviral treatment, the HBV-DNA viral load was undetectable in 12 (92.3%) patients and lower levels of alanine aminotransferase were found in these patients. CONCLUSIONS: Over a 13-year interval, very few individuals infected with HBV were identified, highlighting the barriers for caring for patients with HBV in developing countries. New measures need to be implemented to complement curative practices.

Molecular analysis of methicillin-resistant Staphylococcus aureus dissemination among healthcare professionals and/or HIV patients from a tertiary hospital

Abstract INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) is a nosocomial pathogen in community settings. MRSA colonized individuals may contribute to its dissemination; the risk of MRSA infection is increased in human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) patients, although the prevalence of colonization in this group is not well established. The present study addressed this issue by characterizing MRSA isolates from HIV/AIDS patients and their healthcare providers (HCPs) to determine whether transmission occurred between these two populations. METHODS: A total of 24 MRSA isolates from HIV-infected patients and five from HCPs were collected between August 2011 and May 2013. Susceptibility to currently available antimicrobials was determined. Epidemiological typing was carried out by pulsed-field gel electrophoresis, multilocus sequence typing, and Staphylococcus cassette chromosome (SCCmec) typing. The presence of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) and heterogeneous daptomycin-resistant Staphylococcus aureus (hDRSA) was confirmed by population analysis profile. Isolates characterized in this study were also compared to isolates from 2009 obtained from patients at the same hospital. RESULTS: A variety of lineages were found among patients, including ST5-SCCmecII and ST30-SCCmecIV. Two isolates were Panton-Valentine leukocidin-positive, and hVISA and hDRSA were detected. MRSA isolates from two HCPs were not related to those from HIV/AIDS patients, but clustered with archived MRSA from 2009 with no known relationship to the current study population. CONCLUSIONS: ST105-SCCmecII clones that colonized professionals in 2011 and 2012 were already circulating among patients in 2009, but there is no evidence that these clones spread to or between HIV/AIDS patients up to the 7th day of their hospitalization.

Predictive factors for Leishmania infantum infection in dogs examined at a veterinary teaching hospital in Teresina, State of Piauí, Brazil

Abstract: INTRODUCTION: In Brazil, culling of seropositive dogs is one of the recommended strategies to control visceral leishmaniasis. Since infectiousness is correlated with clinical signs, control measures targeting symptomatic dogs could be more effective. METHODS: A cross-sectional study was carried out among 1,410 dogs, predictive models were developed based on clinical signs and an indirect immunofluorescence antibody test. RESULTS: The validated predictive model showed sensitivity and specificity of 86.5% and 70.0%, respectively. CONCLUSIONS: Predictive models could be used as tools to aid control programs in focusing on a smaller fraction of dogs contributing more to infection dissemination.

The BACTEC MGIT(tm) 320 system as a laboratory tool to diagnose tuberculosis in a Brazilian hospital with a high prevalence of HIV infection

Abstract: INTRODUCTION: The World Health Organization endorses the BACTEC Mycobacterial Growth Indicator Tube (MGIT)(tm) system as a rapid, sensitive, and specific method to diagnostic of tuberculosis. Here, we compared the performance of this system against Ogawa-Kudoh cultures and microscopy. METHODS: A total of 927 samples were obtained between December 2011 and December 2013 from 652 cases of suspected tuberculosis at the School Hospital of the Federal University of Rio Grande in Brazil. RESULTS: The MGIT system confirmed tuberculosis in more cases in less time. CONCLUSIONS: The MGIT system is an effective tool for early diagnosis of tuberculosis, especially in patients with HIV/AIDS.

Secular trends in Klebsiella pneumoniae isolated in a tertiary-care hospital: increasing prevalence and accelerated decline in antimicrobial susceptibility

Abstract: INTRODUCTION Klebsiella pneumoniae has become an increasingly important etiologic agent of nosocomial infections in recent years. This is mainly due to the expression of virulence factors and development of resistance to several antimicrobial drugs. METHODS This retrospective study examines data obtained from the microbiology laboratory of a Brazilian tertiary-care hospital. To assess temporal trends in prevalence and antimicrobial susceptibility, K. pneumoniae isolates were analyzed from 2000 to 2013. The relative frequencies of K. pneumoniae isolation were calculated among all Gram-negative bacilli isolated in each period analyzed. Susceptibility tests were performed using automated systems. RESULTS: From 2000-2006, K. pneumonia isolates comprised 10.7% of isolated Gram-negative bacilli (455/4260). From 2007-2013, this percentage was 18.1% (965/5331). Strictly considering isolates from bloodstream infections, the relative annual prevalence of K. pneumoniae increased from 14-17% to 27-32% during the same periods. A progressive decrease in K. pneumoniae susceptibility to all antimicrobial agents assessed was detected. Partial resistance was also observed to antimicrobial drugs that have been used more recently, such as colistin and tigecycline. CONCLUSIONS Our study indicates that K. pneumoniae has become a major pathogen among hospitalized patients and confirms its recent trend of increasing antimicrobial resistance.

Orifice diseases project - experience of the "Hospital das Clínicas" University of São Paulo Medical Center in day-hospital of anorectal disease

The treatment of malignant or benign colorectal pathologies that require more complex management are priorities in tertiary hospitals such as "Hospital das Clínicas" University of São Paulo Medical Center (HCFMUSP). Therefore, benign, uncomplicated orifice conditions are relegated to second place. The number of patients with hemorrhoids, perianal fistulas, fissures, condylomas and pilonidal cysts who seek treatment at the HFMUSP is very great, resulting in over-crowding in the outpatient clinics and a long waiting list for recommended surgical treatment (at times over 18 months). The authors describe the experience of the HCFMUSP over an eight-day period with day-hospital surgery in which 140 patients underwent surgery. Data was prospectively taken on the patients undergoing surgery for benign orifice pathologies including age, sex, diagnosis, surgery performed, immediate and late postoperative complications, and follow-up. 140 patients operated on over eight days were studied. 68 were males (48.75%) with ages ranging from 25 to 62 (mean 35.2 yrs.). Hemorrhoids was the most frequent condition encountered (82 hemorrhoidectomies, 58.6%), followed by perineal fistula (28 fistula repairs, 20.0%). The most common complication was headache secondary to rachianesthesia occurring in 9 patients (6.4%). One patient (0.7%) developed bleeding immediately PO that required reoperation. Mean follow-up was 104 days. Day-surgery characterized by quality care and low morbidity is feasible in tertiary public hospitals, permitting surgery for benign orifice pathologies on many patients within a short period of time.

Management of pregnancy in a University Hospital: a 6-year study

In order to evaluate the obstetric care in the Obstetric Clinic of the Gynaecology and Obstetrics Department of University of São Paulo, the authors present a survey of the management of pregnancy during the 6-year period from 1993 to 1998. The number of deliveries increased during the study by 45% over the 6 years. During this same period the number of fetal deaths was 526 (4.48%), but there was a significant decrease (p < 0.05) in the incidence of fetal death. However, there was no concomitant increase in the proportion of pregnant women with prenatal care that could explain this improvement. Incidence of premature labor also decreased considerably. The authors believe that the increment in the number of deliveries was due mainly to the increasing number of pregnant women referred to our service. The efforts made by the service towards decreasing the time of hospitalization of both newborns in the nursery and the mothers in the hospital made this possible. Despite the increasing number of deliveries, there was a significant improvement in the management of pregnancy during the period of study. This improvement may be a consequence of the standardization of a protocol of management of pregnancy based on the recent progress in scientific and technological knowledge.

Cost of drugs manufactured by the University Hospital - role of the Central Pharmacy

The hospital pharmacy in large and advanced institutions has evolved from a simple storage and distribution unit into a highly specialized manipulation and dispensation center, responsible for the handling of hundreds of clinical requests, many of them unique and not obtainable from commercial companies. It was therefore quite natural that in many environments, a manufacturing service was gradually established, to cater to both conventional and extraordinary demands of the medical staff. That was the case of Hospital das Clinicas, where multiple categories of drugs are routinely produced inside the pharmacy. However, cost-containment imperatives dictate that such activities be reassessed in the light of their efficiency and essentiality. METHODS: In a prospective study, the output of the Manufacturing Service of the Central Pharmacy during a 12-month period was documented and classified into three types. Group I comprised drugs similar to commercially distributed products, Group II included exclusive formulations for routine consumption, and Group III dealt with special demands related to clinical investigations. RESULTS: Findings for the three categories indicated that these groups represented 34.4%, 45.3%, and 20.3% of total manufacture orders, respectively. Costs of production were assessed and compared with market prices for Group 1 preparations, indicating savings of 63.5%. When applied to the other groups, for which direct equivalent in market value did not exist, these results would suggest total yearly savings of over 5 100 000 US dollars. Even considering that these calculations leave out many components of cost, notably those concerning marketing and distribution, it might still be concluded that at least part of the savings achieved were real. CONCLUSIONS: The observed savings, allied with the convenience and reliability with which the Central Pharmacy performed its obligations, support the contention that internal manufacture of pharmaceutical formulations was a cost-effective alternative in the described setting.

Prevalence rates of infection in intensive care units of a tertiary teaching hospital

OBJECTIVE: To determine the prevalence rates of infections among intensive care unit patients, the predominant infecting organisms, and their resistance patterns. To identify the related factors for intensive care unit-acquired infection and mortality rates. DESIGN: A 1-day point-prevalence study. SETTING:A total of 19 intensive care units at the Hospital das Clínicas - University of São Paulo, School of Medicine (HC-FMUSP), a teaching and tertiary hospital, were eligible to participate in the study. PATIENTS: All patients over 16 years old occupying an intensive care unit bed over a 24-hour period. The 19 intensive care unit s provided 126 patient case reports. MAIN OUTCOME MEASURES: Rates of infection, antimicrobial use, microbiological isolates resistance patterns, potential related factors for intensive care unit-acquired infection, and death rates. RESULTS: A total of 126 patients were studied. Eighty-seven patients (69%) received antimicrobials on the day of study, 72 (57%) for treatment, and 15 (12%) for prophylaxis. Community-acquired infection occurred in 15 patients (20.8%), non- intensive care unit nosocomial infection in 24 (33.3%), and intensive care unit-acquired infection in 22 patients (30.6%). Eleven patients (15.3%) had no defined type. The most frequently reported infections were respiratory (58.5%). The most frequently isolated bacteria were Enterobacteriaceae (33.8%), Pseudomonas aeruginosa (26.4%), and Staphylococcus aureus (16.9%; [100% resistant to methicillin]). Multivariate regression analysis revealed 3 risk factors for intensive care unit-acquired infection: age > 60 years (p = 0.007), use of a nasogastric tube (p = 0.017), and postoperative status (p = 0.017). At the end of 4 weeks, overall mortality was 28.8%. Patients with infection had a mortality rate of 34.7%. There was no difference between mortality rates for infected and noninfected patients (p=0.088). CONCLUSION: The rate of nosocomial infection is high in intensive care unit patients, especially for respiratory infections. The predominant bacteria were Enterobacteriaceae, Pseudomonas aeruginosa, and Staphylococcus aureus (resistant organisms). Factors such as nasogastric intubation, postoperative status, and age ³60 years were significantly associated with infection. This study documents the clinical impression that prevalence rates of intensive care unit-acquired infections are high and suggests that preventive measures are important for reducing the occurrence of infection in critically ill patients.

HIV-1: maternal prognosis

Profound modifications in the profile of patients are currently being observed within the epidemic context of AIDS, especially with respect to pauperization and feminization of the disease. The population most frequently affected is in the reproductive age, and among adults aged 18 to 24 years, the ratio is 1 man to 1 woman, a phenomenon occurring uniformly all over the world. One of the main challenges for HIV-1-infected pregnant women and their doctors is the effect of the interaction between HIV infection and pregnancy. The present article is a review of the literature; and its objective is to assess the influence of HIV-1 infection seen from the maternal perspective, with a discussion of immunologic function, maternal prognosis, and the HIV-abortion interface. At present, we cannot conclude that pregnancy has a short-term effect on the evolution of HIV infection, but the concomitance of HIV and pregnancy may adversely affect the prognosis of gestation, especially in view of its frequent association with increased abortion and puerperal morbidity rates.

Advances in radiochemotherapy in the treatment of head and neck cancer

New advances are being incorporated into the radiochemotherapy treatment of squamous cell carcinoma of the head and neck. Although the overall prognosis is poor in advanced stages, the possibility of incorporating combined protocols of chemotherapy and radiotherapy for organ preservation or for palliation in cases of recurrent/locally advanced stages that are not good surgical candidates must not be forgotten. In this context, there is an urgent need to incorporate quality of life questionnaires and functional evaluation into organ-preservation studies, as well as to assure the importance of surgical salvage after radiotherapy and chemotherapy protocols. The authors provide an extensive review of the advances occurring in the nonsurgical treatment of head and neck cancer. Special attention is given to different radiotherapy protocols, new chemotherapy combinations, molecular markers, and molecular therapy as well as the possibility of incorporating re-irradiation and adjuvant therapy after surgery.

Causes of low vision and use of optical aids in the elderly

PURPOSE: To determine the causes of low vision in an elderly population attended by a university visual rehabilitation service and to check for the use of prescribed optical aids. METHOD: A cross-sectional study was carried out on patients aged 60 years or over attending for the first time a university low vision service in 2001. Ophthalmic reevaluation and interview were performed by means of a structured questionnaire in 2002. RESULTS: The sample comprised 50 subjects aged between 60 and 90 years. Severe low vision (<20/200) was present in 68.0% of patients. The main cause of low vision was age-related macular degeneration (44.0%). Regarding literacy, 16.0% were illiterate and 72.0% had completed fundamental schooling. Thirty-one patients (62.0%) had been prescribed optical aids; 54.8% of these patients stated that they use them. A majority (70.6%) held a favorable opinion of these aids. CONCLUSIONS: The main cause of low vision was age-related macular degeneration. Approximately half of those receiving prescriptions reported actually using the aids in their daily activities. Making best use of residual vision in the elderly population with visual impairment is a priority, given the social context, if the independence necessary for enhanced quality of life is to be achieved.