Study of the risk factors related to acquisition of urinary tract infections in patients submitted to renal transplant

INTRODUCTION: Urinary tract infections (UTI) among transplant recipients are usually caused by gram-negative microorganisms and can provoke a high incidence of morbidity and mortality. The aim of this study was to evaluate the risk factors associated with the acquisition of UTIs during the first year after renal transplantation. METHODS: Here, we report a single-center retrospective cohort study of 99 renal transplant patients followed for the first year after surgery. The definition of a UTI episode was a urine culture showing bacterial growth and leucocyturia when patients presented with urinary symptoms. The absence of infection (asymptomatic bacteriuria) was defined as an absence of symptoms with negative urine culture or bacterial growth with any number of colonies. RESULTS: Ninety-nine patients were included in the study. During the study, 1,847 urine cultures were collected, and 320 (17.3%) tested positive for bacterial growth. Twenty-six (26.2%) patients developed a UTI. The most frequent microorganisms isolated from patients with UTIs were Klebsiella pneumoniae (36%), with 33% of the strains resistant to carbapenems, followed by Escherichia coli (20%). There were no deaths or graft losses associated with UTI episodes. CONCLUSIONS: Among the UTI risk factors studied, the only one that was associated with a higher incidence of infection was female sex. Moreover, the identification of drug-resistant strains is worrisome, as these infections have become widespread globally and represent a challenge in the control and management of infections, especially in solid organ transplantation.

Successful treatment of lower urinary tract infections with oral fosfomycin: a report of three cases

Infections due to multidrug-resistant organisms continue to increase, and therapeutic options remain scarce. Given this challenge, it has become necessary to use older antimicrobials for treatment of these pathogens. We report three patients with lower urinary tract infections caused by Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae who were successfully treated with a seven-day course of oral fosfomycin monotherapy.

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.

Antimicrobial resistance profiles and oxacillinase genes in carbapenem-resistant Acinetobacter baumannii isolated from hospitalized patients in Santa Catarina, Brazil

Abstract: INTRODUCTION: Carbapenems are the therapy of choice for treating severe infections caused by the Acinetobacter calcoaceticus-Acinetobacter baumannii complex. We aimed to assess the prevalence and antimicrobial susceptibility profiles of producers of distinct oxacillinases among nosocomial isolates of the A. calcoaceticus-A. baumannii complex in a 249-bed general hospital located in Joinville, Southern Brazil. METHODS: Of the 139 A. baumannii clinical isolates with reduced susceptibility to carbapenems between 2010 and 2013, 118 isolates from varying anatomical sites and hospital sectors were selected for genotypic analysis. Five families of genes encoding oxacillinases, namely blaOXA-23-like, blaOXA-24-like, blaOXA-51-like, blaOXA-58-like, and blaOXA-143-like, wereinvestigated by multiplex polymerase chain reaction (PCR). RESULTS: Most (87.3%) isolates simultaneously carried the blaOXA-23-likeand blaOXA-51-likegenes, whereas three (2.5%) isolates harbored only blaOXA-51-likeones. The circulation of carbapenem-resistant isolates increased during the study period: from none in 2010, to 22 in 2011, 64 in 2012, and 53 in 2013. CONCLUSIONS: Isolates carrying the blaOXA-23-likeand blaOXA-51-likegenes were widely distributed in the hospital investigated. Because of the worsening scenario, the implementation of preventive measures and effective barriers is needed.

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.

Human herpesvirus 8 (HHV-8) and the etiopathogenesis of Kaposi's sarcoma

OBJECTIVE: To review the current literature on human herpesvirus 8 with particular attention to the aspects related to the etiopathogenesis of Kaposi's sarcoma. MATERIALS AND METHODS: The authors searched original research and review articles on specific aspects of human herpesvirus 8 infection, including virology, epidemiology, transmission, diagnosis, natural history, therapy, and Kaposi's sarcoma etiopathogenesis. The relevant material was evaluated and reviewed. RESULTS: Human herpesvirus 8 is a recently discovered DNA virus that is present throughout the world but with major geographic variation. In the Western world, the virus, transmitted mainly by means of sexual contact, is strongly associated with Kaposi's sarcoma and body cavity-based lymphoma and more controversially with multiple myeloma and other non-proliferative disorders. There is no specific effective treatment, but HIV protease inhibitors may play an indirect role in the clearance of human herpesvirus 8 DNA from peripheral blood mononuclear cells of HIV-infected patients. Human herpesvirus 8 DNA is present in saliva, but there are as yet no documented cases of nosocomial transmission to health care workers. The prevalence of human herpesvirus 8 among health care workers is probably similar to that in the general population. CONCLUSION: Human herpesvirus 8 appears to be, at least in Western Europe and United States, restricted to a population at risk of developing Kaposi's sarcoma. Human herpesvirus 8 certainly has the means to overcome cellular control and immune responses and thus predispose carriers to malignancy, particularly Kaposi's sarcoma. The wide diffusion of Human herpesvirus 8 in classic Kaposi's sarcoma areas appears to represent an important factor in the high incidence of the disease. However, additional co-factors are likely to play a role in the development of Kaposi's sarcoma.

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.

Antimicrobial activity of bergenin from Endopleura uchi (Huber) Cuatrec

Endopleura uchi (Huber) Cuatrec. is an Amazon species traditionally used as treatment for inflammations and female disorders. Bergenin was isolated from ethyl acetate fraction of bark of E. uchi by using column chromatography over sephadex LH-20 and then silica gel 60 flash. Its structure was identified on the basis of its NMR spectra. The antimicrobial activity of bergenin and fractions of methanol extract of E. uchi were evaluated against ATCC microorganisms (Escherichia coli, Salmonella enteritidis, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus, Candida albicans, C. guilliermondii, Aspergillus flavus, A. nidulans). Clinically isolated strains of all of these microorganisms, along with C. tropicalis, A. niger, Shigella sonnei, Serratia marcenses and Klebsiella pneumoniae were also evaluated. The growth inhibition caused by bergenin, extracts and fractions of E. uchi against ATCC microorganisms were similar to the inhibition to microorganisms clinically isolated. The ethyl acetate fraction and the isolate bergenin inhibit the growth of the yeasts C. albicans, C. tropicalis, and C. guilliermondii, but present lower activity against filamentous fungi Aspergillus flavus, A. nidulans, A. niger, and did not inhibit the Gram positive and Gram negative bacteria. The activity of the ethyl acetate fraction and bergenin are in agreement wit its high concentration found in bark extract of E. uchi. Moreover, the selective activity against three Candida species helps to understand its traditional use against infections that affect women.

Infecção de prótese vascular em cirurgia da aorta torácica: revisão da experiência e relato de caso tratado por técnica não convencional

Relatamos o caso de uma paciente de 37 anos de idade, que há cinco anos havia sido submetida à operação de Bental-de Bono em nosso serviço e retornou com dor de forte intensidade no toráx, sendo diagnosticada dissecção aguda de aorta do tipo III e tratada clinicamente. Um ano após esse episódio houve expansão dessa dissecção e a paciente foi submetida à cirurgia com interposição de prótese de dacron em aorta descendente. No pós-operatório imediato houve broncopneumonia esquerda e a paciente recebeu alta em boas condições e afebril. Após um mês da alta, retornou com febre e toxemia. Com diagnóstico de empiema pleural, foi submetida à toracotomia exploradora que não confirmou esse diagnóstico, havendo apenas intenso espessamento pleural. Quatro meses após a toracotomia exploradora, foram isolados Klebsiella pneumoniae e Enterobacter sp na hemocultura. A ressonância magnética revelou imagens compatíveis com infecção peri-prótese. Com esse quadro clínico e laboratorial foi indicada a remoção do enxerto e derivação axilo-bifemoral. A operação foi realizada com sucesso, a paciente recebeu alta em boas condições e continua fazendo controle ambulatorial e, atualmente, encontra-se com 57 meses de evolução sem complicações. São discutidos os métodos empregados para o diagnóstico e tratamento da infecção de prótese na cirurgia da aorta torácica.

Endocardite em válvula de Eustáquio

A endocardite em válvula de Eustáquio é uma condição rara, que ocorre geralmente em usuários de drogas injetáveis e em portadores de marcapasso ou cateter venoso central. Apresentamos um caso de paciente que, em pós-operatório de cirurgia de revascularização do miocárdio com circulação extracorpórea, apresentou endocardite em válvula de Eustáquio diagnosticada pela ecocardiografia, sendo identificada Klebsiella pneumoniae à hemocultura. O paciente foi tratado com antibioticoterapia apropriada, apresentando resolução do quadro em quatro semanas.

The interaction of Gram negative bacteria and S. mansoni in mice with experimental Schistosomiasis

Animals (122 mice) were infected each with eighty cercariae of S. mansoni and subsequently challenged intravenously eight weeks later with the following gram-negative organisms. S. typhi, E. coli, Klebsiella-enterobacter species, Proteus mirabilis and Pseudomonas aeruginosa. Enumeration of bacteria in the liver, spleen and blood and S. mansoni from the portal sistem was performed from one to four weeks later in infected animals. A significant difference between infection produced by S. typhi and other gram negative organisms was observed: S. typhi persisted longer in the spleen and liver and could be recovered from S. mansoni worms up to three weeks following bacterial infection. Other gram negative bacteria disappeared from S. mansoni worms after two weeks of initial challenge. Additional animals (51 mice) infected with S. mansoni were given S. typhi, E. coli or sterile saline. After two weeks, animals were sacrificed and the recovery rate of worms from the portal system, and the mesenteric and hepatic oogram were determined. in animals infected with E. coli a significant decrease in the number of worms was observed compared to the saline control group; thirty worms were recovered in the control group compared to two worms in e. coli infected animals. In addition, the patterns of oviposition was significantly different in these latter animals suggesting complete inhibition of this process. Following S. typhi infection the difference in recovery of worms and pattern of oviposition was minimal. These findings suggest a difference in the interaction of various gram negative bacteria and S. mansoni and are consistent with the clinical observation of prolonged salmonella bacteremia in patients with schistosomiasis.

Bactérias gram negativas resistentes a antimicrobianos em alimentos

A partir de 154 espécimens de alimentos, representados por hortaliças (alface), leite e merenda escolar, obteve-se o isolamento e identificação de 400 amostras de bacilos Gram negativos. Esta amostragem se distribuiu em 339 enterobactérias (Escherichia, Shigella, Citrobacter, Klebsiella, Enterobacter, Serratia e Proteus) e 61 de gêneros afins (Acinetobacter, Flavobacterium, Aeromonas e Pseudomonas). Submetendo-se as culturas aos antimicrobianos: sulfadiazina (Su), estreptomicina (Sm), tetraciclina (Tc), cloranfenicol (Cm), canamicina (Km), ampicilina (Ap), ácido nalidíxico (Nal) e gentamicina (Gm), observou-se apenas seis estirpes sensíveis a todas as drogas e sensibilidade absoluta à Gm. A predominância dos modelos Su (27,6%) e Su-Ap (39,6%) incidiu nas enterobactérias, enquanto que, 18,0% para Ap e 9,8% para Su-Ap foram detectados nos gêneros afins. Para caracterização da resistência foram realizados testes de conjugação e a totalidade das culturas não revelou transferência para o gene que confere resistência ao ácido nalidíxico. Relevantes são as taxas de amostras R+ observadas nos bacilos entéricos, oscilando em torno de 90% (leite e merenda escolar) e alface, em torno de 70%

Immunomodulation by microbial ribosomes

Over the past twenty years, many authors have reported evidence of the immunoprotective capacity of ribosomes isolated from bacteria, fungi and parasites. Since 1971 we have explored the protective capacity of ribosomes isolated from a large variety of microorganisms responsible for human and animal diseases. More recently, using monoclonal antibodies raised against ribosomes and then selected for their ability to confer passive immunity to mice, we have studied the mechanism of the protection induced by ribosomes. These studies, in parallel with the development of a technology for the large scale production of ribosomes, have allowed us to achieve a new regard for ribosomal vaccines for use in human. The general concept of ribosomal vaccines in presented and examples of two such vaccines are described with data on the specific protection that they induce in mice against experimental infections with Klebsiella peneumoniae, Streptococcus pneumoniae, S. pyogenes and Haemophilus influenzae for the first one, and against Candida albicans type A and type B for the second one. Because of their high immunogenicity and their innocuity these vaccines represent a decisive improvement over classical microbial vaccines.

In vitro cell activating properties of the composite ribosomal vaccine D53

D53 (RibomuntyR) is a composite vaccine made of immunogenic ribosomes from 4 bacterial species (Klebsiella pneumoniae, Haemophilus influenzae, Streptococcus pyogenes and Streptococcus pneumoniae) associated with a membrane proteoglycan from a non encapsulated strain of Klebsiella pneumoniae. D53 is a potent inducer of interleukin-1 production by mouse BALB/c spleen cells as shown by the C3H/HeJ thymocyte co-stimulation assay. Furthermore D53 triggers DNA synthesis by mouse spleen cells and induces the maturation of B lymphocytes into immunoglobulin secreting cells. Polyclonal B cell activation by D53 was readily achieved in the C3H/HeJ strain which is deficient in its response to E. coli lipopolysaccharide. The proliferative response to D53 was abrogated by removal of B cells from the spleen cell suspension, but it was not altered after depletion of T cells or adherent cells. D53 induced polyclonal B cell activation of spleen cells from athymic nude mice and from CBA/N mice. Each component of D53 induced polyclona B cell activation except ribosomes from Streptococcus pneumoniae. Each triggered Interleukin-1 synthesis except ribosomes from Klebsiella penumoniae. These in vitro properties may account for some of the in vivo immunostimulating properties of this composite vaccine.

Use of a selective medium with potassium tellurite to follow intestinal colonization of hospitalized patients by drug-resistant Enterobacteriaceae

Nosocomial infections are a relevant factor in complicating the recovery of patients interned for even minor causes. In attempt to determine their origin it is crucial to consider that their origin is of an endogenous nature. Looking for an acessible expression of intestinal colonization we analyzed fecal samples from 3 separate groups of hospital patients collected after different lenghts of time. For practical reasons one group was studied prospectively and two other groups (patients hospitalized for up to 7 days and patients hospitalized for more than 7 days) were compared to one another. We looked for the emergence of tellurite resistance among Enterobacteriaceae using a selective medium. MacConkey potassium tellurite (MCPT). The frequence of prospectively studied patients with tellurite resistant strains was significantly greater after 7 days of hospitalization. For the two other groups, patients with more than 7 days of hospitalization showed a significant increase of bacterial species and of strains with new antimicrobial resistance markers. High molecular weigth plasmids were detected in some of these strains. These data show that the MCPT medium is a useful tool for the investigation of bowel colonization in hospitalized patients by drug-resistant Enterobacteriaceae.