Resumo em Inglês:

BACKGROUND: A number of studies have reported on the effectiveness of sulbactam-based therapies for Acinetobacter baumannii infection; however, there is little evidence that sulbactam-based therapies are more or less effective than alternative therapies. Unfortunately, there is a distinct lack of high quality data (i.e., from randomized controlled trials) available on this issue. Therefore, we conducted a systematic review and meta-analysis comparing the efficacy of sulbactam-based and non-sulbactam-based regimens in the treatment of A. baumannii infection. METHODS: We searched PubMed, MEDLINE, Biomedical Central, Google Scholar, the China National Knowledge Infrastructure, the Cochrane library, and the Directory of Open Access using the terms "sulbactam and baumannii" or "maxtam and baumannii". Randomized controlled trials, controlled clinical studies, and cohort studies were considered for inclusion. The primary outcome was the clinical response rate for sulbactam-based therapy vs comparator therapies. RESULTS: Four studies (1 prospective, 3 retrospective) were included in the metaanalysis. Sulbactam was given in combination with ampicillin, carbapenem, or cefoperazone (n = 112 participants). Comparator drugs included colistin, cephalosporins, anti-pseudomonas penicillins, fluoroquinolones, minocycline/doxycycline, aminoglycosides, tigecycline, polymyxin, imipenem/cilastatin, and combination therapy (n = 107 participants). The combined clinical response rate odds ratio did not significantly favor sulbactam-based therapy over comparator therapy (odds ratio = 1.054, 95% confidence interval = 0.550-2.019, p = 0.874), nor did any of the individual study odds ratios. CONCLUSIONS: The available evidence suggests that sulbactam-based therapy may be similarly efficacious to alternative antimicrobial therapies for the treatment of A. baumannii infection. Further research on this issue is warranted given the limited availability of data from high quality/randomized controlled trials.

Resumo em Inglês:

Biofilms formed by Candida albicans, a human pathogen, are known to be resistant to different antifungal agents. Novel strategies to combat the biofilm associated Candida infections like multiple drug therapy are being explored. In this study, potential of chloroquine to be a partner drug in combination with four antifungal agents, namely fluconazole, voriconazole, amphotericin B, and caspofungin, was explored against biofilms of C. albicans. Activity of various concentrations of chloroquine in combination with a particular antifungal drug was analyzed in a checkerboard format. Growth of biofilm in presence of drugs was analyzed by XTT-assay, in terms of relative metabolic activity compared to that of drug free control. Results obtained by XTT-metabolic assay were confirmed by scanning electron microscopy. The interactions between chloroquine and four antifungal drugs were determined by calculating fractional inhibitory concentration indices. Azole resistance in biofilms was reverted significantly (p < 0.05) in presence of 250 µg/mL of chloroquine, which resulted in inhibition of biofilms at very low concentrations of antifungal drugs. No significant alteration in the sensitivity of biofilms to caspofungin and amphotericin B was evident in combination with chloroquine. This study for the first time indicates that chloroquine potentiates anti-biofilm activity of fluconazole and voriconazole.

Resumo em Inglês:

Children with cerebrospinal fluid pleocytosis are frequently treated with parenteral antibiotics, but only a few have bacterial meningitis. Although some clinical prediction rules, such as bacterial meningitis score, are of well-known value, the cerebrospinal fluid white blood cells count can be the initial available information. Our aim was to establish a cutoff point of cerebrospinal fluid white blood cell count that could distinguish bacterial from viral and aseptic meningitis. A retrospective study of children aged 29 days to 17 years who were admitted between January 1st and December 31th, 2009, with cerebrospinal fluid pleocytosis (white blood cell > 7 µL-1) was conducted. The cases of traumatic lumbar puncture and of antibiotic treatment before lumbar puncture were excluded. There were 295 patients with cerebrospinal fluid pleocytosis, 60.3% females, medium age 5.0 ± 4.3 years distributed as: 12.2% 1-3 months; 10.5% 3-12 months; 29.8% 12 months to 5 years; 47.5% >5 years. Thirty one children (10.5%) were diagnosed with bacterial meningitis, 156 (52.9%) viral meningitis and 108 (36.6%) aseptic meningitis. Bacterial meningitis was caused by Neisseria meningi tidis (48.4%), Streptococcus pneumoniae (32.3%), other Streptococcus species (9.7%), and other agents (9.7%). cerebrospinal fluid white blood cell count was significantly higher in patients with bacterial meningitis (mean, 4839 cells/µL) compared to patients with aseptic meningitis (mean, 159 cells/µL, p < 0.001), with those with aseptic meningitis (mean, 577 cells/µL, p < 0.001) and with all non-bacterial meningitis cases together (p < 0.001). A cutoff value of 321 white blood cell/µL showed the best combination of sensitivity (80.6%) and specificity (81.4%) for the diagnosis of bacterial meningitis (area under receiver operating characteristic curve 0.837). Therefore, the value of cerebrospinal fluid white blood cell count was found to be a useful and rapid diagnostic test to distinguish between bacterial and nonbacterial meningitis in children.

Resumo em Inglês:

The aim of the present study was to verify the association between seropositivity for IgG anti-Toxoplasma gondii antibodies and social, economic and environmental variables of pregnant women attending the public health centers of Paraná, Brazil. From January 2007 to July 2010, 2226 pregnant women were interviewed and detection of anti-T. gondii specific IgG and IgM antibodies was performed by chemiluminescence test. Seropositivity for anti-T. gondii IgG was observed in 1151 (51.7%) pregnant women, 29 of which (1.3%) presented IgM reagent with IgG of high avidity. The variables associated with the presence of IgG were residency in the rural area, more than one pregnancy, less than or equal to eight years schooling, low per capita income, age group, raw or poorly cooked meat ingestion, and contact with the soil. There was neither association with raw fruit and vegetable ingestion nor with the presence of cats in the residencies.

Resumo em Inglês:

BACKGROUND: Mitogen-activated protein kinase (MAPK) signaling pathway plays an important role in response to viral infection. The aim of this study was to explore the function and mechanism of MAPK signaling pathway in enterovirus 71 (EV71) infection of human rhabdomyosarcoma (RD) cells. METHODS: Apoptosis of RD cells was observed using annexin V-FITC/PI binding assay under a fluorescence microscope. Cellular RNA was extracted and transcribed to cDNA. The expressions of 56 genes of MAPK signaling pathway in EV71-infected RD cells at 8 h and 20 h after infection were analyzed by PCR array. The levels of IL-2, IL-4, IL-10, and TNF-α in the supernatant of RD cells infected with EV71 at different time points were measured by ELISA. RESULTS: The viability of RD cells decreased obviously within 48 h after EV71 infection. Compared with the control group, EV71 infection resulted in the significantly enhanced releases of IL-2, IL-4, IL-10 and TNF-α from infected RD cells (p < 0.05). At 8 h after infection, the expressions of c-Jun, c-Fos, IFN-i, MEKK1, MLK3 and NIK genes in EV71-infected RD cells were up-regulated by 2.08-6.12-fold, whereas other 19 genes (e.g. AKT1, AKT2, E2F1, IKK and NF-κB1) exhibited down-regulation. However, at 20 h after infection, those MAPK signaling molecules including MEKK1, ASK1, MLK2, MLK3, NIK, MEK1, MEK2, MEK4, MEK7, ERK1, JNK1 and JNK2 were up-regulated. In addition, the expressions of AKT2, ELK1, c-Jun, c-Fos, NF-κB p65, PI3K and STAT1 were also increased. CONCLUSION: EV71 infection induces the differential gene expressions of MAPK signaling pathway such as ERK, JNK and PI3K/AKT in RD cells, which may be associated with the secretions of inflammatory cytokines and host cell apoptosis.

Resumo em Inglês:

The aim of this study was to conduct a cost-utility study of adefovir, entecavir, interferon alpha, pegylated interferon alpha, lamivudine and tenofovir for chronic hepatitis B in the context of Brazilian Public Health Care System. A systematic review was carried out for efficacy and safety. Another review was performed to collect utility data and transition probabilities between health states. A Markov model was developed in a time horizon of 40 years with annual cycles for three groups of: HBeAg positive, HBeAg negative, and all patients. These strategies were compared to a fourth group that received no treatment. Discount rates of 5% were applied and sensitivity analyses were performed. Tenofovir offered the best cost-utility ratio for the three evaluated models: U$397, U$385 and U$384 (per QALY, respectively, for HBeAg positive, negative, and all patients). All other strategies were completely dominated because they showed higher costs and lower effectiveness than tenofovir. The sequence of cost-utility in the three models was: tenofovir, entecavir, lamivudine, adefovir, telbivudine, pegylated interferon alpha, and interferon alpha. In the sensitivity analysis, adefovir showed lower cost-utility than telbivudine in some situations. The study has some limitations, primarily related to the creation of scenarios and modeling. In this study, tenofovir presented the best cost-utility ratio. The results obtained in this study will be valuable in decision-making and in the review of the clinical protocol, mainly involving the allocation of available resources for health care.

Resumo em Inglês:

OBJECTIVES: To evaluate the clinical effects of blood purification for treating fulminant hepatic failure (FHF). METHODS: Thirty-three severe FHF patients with hepatic encephalopathy (HE) above grade III were subjected to a combined blood purification treatment in addition to the comprehensive liver protection therapy. Patients underwent continuous hemofiltration on a daily basis during the daytime followed by sequential treatment with plasma exchange or hemodialysis every 2-3 days. The therapeutic effects of this treatment were evaluated. RESULTS: After treatment with blood purification, restoration of consciousness (those who abandoned the treatment without restoration of consciousness were excluded) was achieved in 6 of 8 cases (75%) in acute liver failure (ALF) group, 3 of 3 cases (100%) in subacute liver failure (SALF) group, and 9 of 14 cases (64.29%) in acute/subacute on chronic liver failure (A/SCLF) group. Of all cases, 11 patients restored consciousness after 7 days in a coma. The rate of long-term survival (those who abandoned the treatment were excluded) was 3/7 (42.86%) for ALF group, 2/2 (100%) for SALF group, and 1/11 (9.09%) for A/SCLF group. The levels of hemoglobin and platelet in peripheral blood were significantly reduced after blood purification. CONCLUSIONS: Treatment of FHF patients with daily continuous hemofiltration during the daytime is effective in treating HE and in improving health status in the early stages of the disease. Long-term prognosis also benefits from this treatment. The rate of consciousness recovery and long-term survival is highest in SALF group followed by ALF group. This treatment is less effective in A/SCLF patients. It should be noted that blood purification procedure may cause damage to blood cells.

Resumo em Inglês:

OBJECTIVES: To study the potential factors include gene mutation, efflux pump and alteration of permeability associated with quinolone-resistance of Salmonella enterica strains isolated from patients with acute gastroenteritis and to evaluate the degree of synergistic activity of efflux pump inhibitors when combined with ciprofloxacin against resistant isolates. METHODS: Antimicrobial resistance patterns of fifty-eight Salmonella isolates were tested. Five isolates were selected to study the mechanism of resistance associated with quinolone group, including mutation in topoisomerase-encoding gene, altered cell permeability, and expression of an active efflux system. In addition, the combination between antibiotics and efflux pump inhibitors to overcome the microbial resistance was evaluated. RESULTS: Five Salmonella isolates totally resistant to all quinolones were studied. All isolates showed alterations in outer membrane proteins including disappearance of some or all of these proteins (Omp-A, Omp-C, Omp-D and Omp-F). Minimum inhibitory concentration values of ciprofloxacin were determined in the presence/absence of the efflux pump inhibitors: carbonyl cyanide m-chlorophenylhydrazone, norepinephrin and trimethoprim. Minimum inhibitory concentration values for two of the isolates were 2-4 fold lower with the addition of efflux pump inhibitors. All five Salmonella isolates were amplified for gyrA and parC genes and only two isolates were sequenced. S. Enteritidis 22 had double mutations at codon 83 and 87 in addition to three mutations at parC at codons 67, 76 and 80 whereas S. Typhimurium 57 had three mutations at codons 83, 87 and 119, but no mutations at parC. CONCLUSIONS: Efflux pump inhibitors may inhibit the major AcrAB-TolC in Salmonella efflux systems which are the major efflux pumps responsible for multidrug resistance in Gramnegative clinical isolates.

Resumo em Inglês:

OBJECTIVE: To evaluate the cumulative incidence of dyslipidemia and fasting glucose impairment three years after initiating the first antiretroviral (ART) regimen and the association with the type of ART regimen in an AIDS outpatient clinic in Brazil. METHODS: Retrospective cohort of HIV-1 infected patients attending an outpatient HIV clinic in Vitoria, Brazil, between January/2010 and May/2011. Data, including blood pressure, dyslipidemia (high total cholesterol and low HDL-C), fasting glucose, and cardiovascular risk by Framingham Risk Score were abstracted from medical records from clinic visits six months prior and three years after starting ART. We assessed independent associated factors for dyslipidemia using multiple logistic regression. RESULTS: Four hundred and ninety-eight patients on ART were studied. Median age was 45 years (interquartile range (IQR): 37-52), and median time since HIV diagnosis was 7.7 years (IQR: 3.8-10.0). The proportion of patients with dyslipidemia was 22.3% (95% CI: 18.6-25.9%) 36 months after ART initiation. Triglycerides levels >150 mg/dL (55.2% vs. 25.4%, p = 0.021) and high fasting glucose (5.8% vs. 2.3%, p = 0.034) were diagnosed more frequently after ART use when compared to baseline values. Multiple logistic regression analysis has shown dyslipidemia to be associated with lopinavir/r use [OR = 1.74 (95% CI: 1.12-2.86)]. CONCLUSION: These data show high chance of dyslipidemia after initiation of ART. Long-term follow-up will help identify the impact of ART on cardiovascular risk.

Resumo em Inglês:

OBJECTIVE: To study whether patients with HIV-1 associated lipodystrophy (LD) on highly active antiretroviral treatment (HAART) have more psychopathology and worse psychosocial adjustment than a similar group without this syndrome. METHODS: In a cross-sectional, observational study we compared 47 HIV-1 infected patients with LD (LD group) with 39 HIV-1 infected patients without LD (non-LD group). All participants were on HAART. The Beck Depression Inventory (BDI), the State and Trait Anxiety Inventory (STAI) and the Goldberg Health Questionnaire (GHQ-60) were administered. Levels of familial, work and social adjustment and adjustment to stressful events were evaluated in a semi-structured interview. Clinical information was extracted from the clinical records. RESULTS: In the univariate analysis patients with LD showed higher state anxiety scores (p = 0.009) and worse work adjustment (p = 0.019) than those without LD. A total of 45.3% of LD patients scored above the cut-off point on the trait anxiety scale, and over 33.3% scored above the cut-off point on the BDI, GHQ and state anxiety scales. However, in multivariate analyses LD was not independently associated with psychopathology or with worse adjustment in the studied areas. CONCLUSIONS: The finding that LD was not a predictor of greater psychopathology or worse psychosocial adjustment in HIV-1 infected patients, despite the high scores found, suggests that factors not taken into account in this study, such as LD severity and self-perception should have been included in the analysis. Further studies including a greater number of variables and a larger sample size will advance our understanding of this complex condition.

Resumo em Inglês:

OBJECTIVE: We report an outbreak of Achromobacter xylosoxidans at a neonatal intensive care unit. We aimed to present clinical, laboratory and treatment data of the patients. Materials and METHODS: All consecutive episodes of bacteremia due to A. xylosoxidans at our neonatal intensive care unit, beginning with the index case detected at November 2009 until cessation of the outbreak in April 2010, were evaluated retrospectively. RESULTS: Thirty-four episodes of bacteremia occurred in 22 neonates during a 6-month period. Among the affected, 90% were preterm newborns with gestational age of 32 weeks or less and 60% had birth weight of 1000 g or less. Endotracheal intubation, intravenous catheter use, total parenteral nutrition and prolonged antibiotic therapy were the predisposing conditions. Presenting features were abdominal distention, thrombocytopenia and neutropenia. The mortality rate was 13.6% and the majority of isolates were susceptible to piperacillin-tazobactam, carbapenems and trimethoprim-sulfametoxazole, and resistant to gentamycin. More than half were breakthrough infections. Despite intensive efforts to control the outbreak by standard methods of hand hygiene, patient screening and isolation, containment could be achieved only after the neonatal intensive care unit was relocated. The investigation was not able to single out the source of the outbreak. CONCLUSION: A. xylosoxidans has the potential to cause serious infections in premature babies. More studies are needed to determine the importance of different sources of infection in hospital units.

Resumo em Inglês:

The hepatitis C virus and human immunodeficiency virus share the same transmission routes, which makes co-infection an unfavorable condition for the natural history of both viral diseases. In this context, it should be highlighted that the knowledge of the extent of co-infection and associated risk factors is a vital tool for prevention and control over infectious diseases. The aim of this study was to review the literature, seeking to examine the prevalence of human immunodeficiency virus/hepatitis C virus co-infection reported in studies conducted in Brazil, and identify the main risk factors associated with co-infection. The electronic search was conducted in the Medline, Lilacs and SciELO databases. The following keywords were used: human immunodeficiency virus and Hepatitis C or hepatitis C virus and Brazil. The search led to 376 articles, of which 69 were selected for data extraction. We excluded animal studies, reports or case series, review articles, letters to the editor, other types of hepatitis and those studies in which co-infected patients were intentionally selected for comparison to single infected individuals. As a result, 40 articles were reviewed. The majority of the population in these studies was male (71%) and young adults, with a mean age of 26.7 years. The prevalence of hepatitis C virus co-infection among individuals living with human immunodeficiency virus in the studies conducted in Brazil ranged from 3.3% (serum samples) to 82.4% (drug users), with an average of 20.3%. The findings reveal that the prevalence of human immunodeficiency virus/hepatitis C virus co-infection is highly variable, depending on the characteristics of the study population. Risk factors associated with human immunodeficiency virus/hepatitis C virus co-infection were injection drug use and blood transfusion.

Resumo em Inglês:

The worldwide elderly population is expected to grow by an additional 694 million people by 2025. By that time, there will be approximately two billion elderly people in the world, most of whom (80%) will be living in developing countries. Based on recent estimates, this population will number over 40 million in 2030 in Brazil and a consequent increase in governmental spending for this population can be expected. Since highly active antiretroviral therapy became available in the mid-1990s, the life expectancy of people living with HIV has increased significantly. Approximately 12 million life years were added to the world between 1996 and 2008 as a consequence of wider access to highly active antiretroviral therapy. In Brazil, the incidence of AIDS among the population aged >50 years doubled between 1996 and 2006. The development of antiretroviral therapy has allowed individuals diagnosed at a younger age to live longer, which partially explains the aging tendency associated with the HIV/AIDS epidemic. It is estimated that by 2015, subjects aged >50 years will represent 50% of the people living with HIV undergoing clinical treatment. This scenario presents some challenges, including the fact that the diagnosis of HIV tends to be delayed in older patients compared to younger patients because the symptoms of HIV can be confused with those of other common diseases among the elderly and also because healthcare professionals do not consider this population to be at high risk for HIV infection. In regard to the individuals diagnosed with HIV, a further challenge is presented by the morbidity normally associated with aging. Finally, the elderly also exhibit higher susceptibility to the toxic effects and pharmacological interactions of medications. The present article reviews the literature regarding the profile of HIV infection among individuals aged >50 years focusing on practical features related to the clinical approach and long-term follow-up of this population.

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The objective of this study was to investigate bacterial resistance trends, infection sites and the relationship between resistance and admittance to the intensive care unit (ICU). A total of 53,316 bacteria identified between 1999 and 2008 were evaluated. Multidrug resistance was characterized when gram-negative bacilli (GNB) presented resistance to two or more classes of antibiotics. Gram-positive cocci (CPC) were assessed for resistance to penicillin, oxacillin and vancomycin. GNB were the most common (66.1%) isolate. There was a 3.7-fold overall increase in multidrug resistant GNB over the study period; Acinetobacter baumanii and Staphylococcus aureus were the most prevalent. Highest increases were recorded for Kleb siella pneumoniae (14.6-fold) and enterococci (73-fold). The resistance rates for GNB and GPC were 36% and 51.7%, respectively. Most multidrug resistant GNB and GPC were recovered from ICU patients (p-value < 0.001). vancomycin-resistant enterococci were isolated during this decade with an increase of 18.7% by 2008. these data confirm the worldwide trend in multidrug bacterial resistance.

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Combination therapy of CT-guided percutaneous drainage and antibiotics is the first-line treatment for abscesses. Its effectiveness has been demonstrated. However, the therapeutic impact of this procedure for infection treatment has never been reported. We retrospectively analyzed all 47 patients who received CT-guided percutaneous drainage for infection treatment. Patients' characteristics, pathogens isolated, antibiotics administered, technical and clinical outcomes, complications related to this procedure and therapeutic impacts were investigated. Patients were 26 males and 21 females. The mean age was 63.5 years (±18.7). The diseases targeted were 19 retroperitoneal abscesses, 18 intraabdominal abscesses, three pelvic abscesses, and seven others. As for technical outcomes, all of the 54 procedures (100%) were successful. As for clinical outcomes, 44 (93.6%) were cured and three patients (6.4%) died. No complications related to this procedure were found in this study. A total of 42 patients (88%) had a change in the management of their infection as a result of CT-guided percutaneous drainage, such as selection and discontinuation of antibiotics. In conclusion, CT-guided percutaneous drainage is a safe and favorable procedure in the treatment of deep tissue abscesses. Therapeutic impact of these procedures helped physicians make a rational decision for antibiotics selection.

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Antimicrobial treatment is often indicated to neutropenic patients. Although renal failure is a common complication of many antibiotics, no information could be found in the literature defining which are the best screening criteria for detecting renal injury. In this paper, the authors aim to assess the progress to renal failure in neutropenic patients on antimicrobial use and to compare different diagnostic criteria of renal failure in association to antimicrobial agents used. This is a cohort study conducted from February to August 2006 at the Hospital das Clínicas of the Universidade Federal de Minas Gerais, which included patients with neutropenia and antimicrobial therapy for the treatment of Healthcare Associated Infections notified by the Hospital Infection Control Committee. Renal injury has ensued in 25% of patients and no statistical difference between distinct criteria for renal injury was observed. Association of greater number of antimicrobials was associated with renal impairment. Time required for renal injury was independent of the antimicrobial regimen used, but mortality among patients with renal injury was higher when compared to those who had preserved renal function.

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Lemierre syndrome is characterized by acute septic thrombophlebitis of the internal jugular vein (IJV) that develops after an oropharyngeal infection, and can be complicated by septic emboli to lungs and other organs. The most frequent causative agent is Fusobacterium necrophorum, an anaerobic bacillus found in normal oropharyngeal flora. Staphylococcus aureus has emerged as a cause of Lemierre syndrome in the last decade. We report a case of a 24-year-old man who developed septic IJV thrombosis and necrotizing pneumonia due to S. aureus from an infected hematoma in the right sternocleidomastoid muscle. Antibiotics are the mainstay of therapy with few cases needing anticoagulation. A good outcome is dependent upon an awareness of the condition, a high index of suspicion, and prompt initiation of antibiotic therapy. Recognition of S. aureus as a cause of Lemierre syndrome can guide the choice of initial antibiotics to cover this virulent pathogen.