Ceftriaxone acts synergistically with levofloxacin in experimental meningitis and reduces levofloxacin-induced resistance in penicillin-resistant pneumococci.

Ceftriaxone acted synergistically with levofloxacin in time-killing assays in vitro over 8 h against two penicillin-resistant pneumococcal strains (WB4 and KR4; MIC of penicillin: 4 mg/L). Synergy was confirmed with the chequerboard method, showing FIC indices of 0.25. In the experimental rabbit meningitis model, ceftriaxone (1x 125 mg/kg) was slightly less bactericidal (-0.30 Deltalog(10) cfu/mL(.)h) compared with levofloxacin (-0.45 Deltalog(10) cfu/mL(.)h) against the penicillin-resistant strain WB4. The combination therapy (levofloxacin and ceftriaxone) was significantly superior (-0.64 Deltalog(10) cfu/mL(.)h) to either monotherapy. In cycling experiments in vitro, the addition of ceftriaxone at a sub-MIC concentration (1/16 MIC) reduced levofloxacin-induced resistance in the two strains KR4 and WB4. After 12 cycles with levofloxacin monotherapy, the MIC increased 64-fold in both strains versus a 16-fold increase with the combination (levofloxacin + ceftriaxone 1/16 MIC). In both strains, levofloxacin-induced resistance was confirmed by mutations detected in the genes parC and gyrA, encoding for subunits of topoisomerase IV and gyrase, respectively. The addition of ceftriaxone suppressed mutations in parC but led to a new mutation in parE in both strains.

Biomphalaria tenagophila: dominant character of the resistance to Schistosoma mansoni in descendants of crossbreedings between resistant (Taim, RS) and susceptible (Joinville, SC) strains

The aim of the present work was to study parasitological, molecular, and genetic aspects in descendants of crossbreedings between a totally resistant Biomphalaria tenagophila strain (Taim, RS) and another one highly susceptible (Joinville, SC) to Schistosoma mansoni. Descendants F1 and F2 were submitted to S. mansoni infection (LE strain). The susceptibility rates for individuals from Group F1 were 0 to 0.6%, and from Group F2 was 7.2%. The susceptible individuals from Group F2 discharged a lower number of cercariae, when compared with the susceptible parental group, and in 2 out of 9 positive snails the cercarial elimination was discontinued. In order to identify genetic markers associated with resistance the genotype of parental snails and their offspring F1 and F2 were analyzed by means of the randomly amplified polymorphic DNA method. Nevertheless, it was not possible to detect any marker associated to resistance, but the results showed that in the mentioned species the resistance character is determined by two dominant genes.

Variation of snail's abundance in two water bodies harboring strains of Pseudosuccinea columella resistant and susceptible to Fasciola hepatica miracidial infection, in Pinar del Río Province, Cuba

The abundance of freshwater snails in two rural sites of Pinar del Río, Cuba, which harbor Pseudosuccinea columella susceptible and resistant to miracidia of Fasciola hepatica was followed for one year. Susceptible snails were found in the most anthropic site (IPA) whereas the resistant population inhabited the most preserved one (El Azufre). Only two snail species coexisted with P. columella at IPA site (Physa cubensis and Tarebia granifera) while five species were found at El Azufre, including an endemic from that province (Hemisinus cubanianus). Populations of both resistant and susceptible snails showed stable densities throughout the year, although the susceptible strain attained higher abundance. The highest densities were observed in April-May 2004 for the susceptible population whereas the resistant strain attained its highest abundance in January 2004. No record of Fossaria cubensis was made and the thiarid T. granifera occurred only at low densities. One of the sampled sites (IPA) meets all the conditions for the first report of P. columella naturally infected with larvae of F. hepatica.

Vascular-endothelial-growth-factor (VEGF) targeting therapies for endocrine refractory or resistant metastatic breast cancer.

BACKGROUND: Vascular-endothelial-growth-factor (VEGF) is a key mediator of angiogenesis. VEGF-targeting therapies have shown significant benefits and been successfully integrated in routine clinical practice for other types of cancer, such as metastatic colorectal cancer. By contrast, individual trial results in metastatic breast cancer (MBC) are highly variable and their value is controversial. OBJECTIVES: To evaluate the benefits (in progression-free survival (PFS) and overall survival (OS)) and harms (toxicity) of VEGF-targeting therapies in patients with hormone-refractory or hormone-receptor negative metastatic breast cancer. SEARCH METHODS: Searches of CENTRAL, MEDLINE, EMBASE, the Cochrane Breast Cancer Group's Specialised Register, registers of ongoing trials and proceedings of conferences were conducted in January and September 2011, starting in 2000. Reference lists were scanned and members of the Cochrane Breast Cancer Group, experts and manufacturers of relevant drug were contacted to obtain further information. No language restrictions were applied. SELECTION CRITERIA: Randomised controlled trials (RCTs) to evaluate treatment benefit and non-randomised studies in the routine oncology practice setting to evaluate treatment harms. DATA COLLECTION AND ANALYSIS: We performed data collection and analysis according to the published protocol. Individual patient data was sought but not provided. Therefore, the meta-analysis had to be based on published data. Summary statistics for the primary endpoint (PFS) were hazard ratios (HRs). MAIN RESULTS: We identified seven RCTs, one register, and five ongoing trials from a total of 347 references. The published trials for VEGF-targeting drugs in MBC were limited to bevacizumab. Four trials, including a total of 2886 patients, were available for the comparison of first-line chemotherapy, with versus without bevacizumab. PFS (HR 0.67; 95% confidence interval (CI) 0.61 to 0.73) and response rate were significantly better for patients treated with bevacizumab, with moderate heterogeneity regarding the magnitude of the effect on PFS. For second-line chemotherapy, a smaller, but still significant benefit in terms of PFS could be demonstrated for patients treated with bevacizumab (HR 0.85; 95% CI 0.73 to 0.98), as well as a benefit in tumour response. However, OS did not differ significantly, neither in first- (HR 0.93; 95% CI 0.84 to 1.04), nor second-line therapy (HR 0.98; 95% CI 0.83 to 1.16). Quality of life (QoL) was evaluated in four trials but results were published for only two of these with no relevant impact. Subgroup analysis stated a significant greater benefit for patients with previous (taxane) chemotherapy and patients with hormone-receptor negative status. Regarding toxicity, data from RCTs and registry data were consistent and in line with the known toxicity profile of bevacizumab. While significantly higher rates of adverse events (AEs) grade III/IV (odds ratio (OR) 1.77; 95% CI 1.44 to 2.18) and serious adverse events (SAEs) (OR 1.41; 95% CI 1.13 to 1.75) were observed in patients treated with bevacizumab, rates of treatment-related deaths were lower in patients treated with bevacizumab (OR 0.60; 95% CI 0.36 to 0.99). AUTHORS' CONCLUSIONS: The overall patient benefit from adding bevacizumab to first- and second-line chemotherapy in metastatic breast cancer can at best be considered as modest. It is dependent on the type of chemotherapy used and limited to a prolongation of PFS and response rates in both first- and second-line therapy, both surrogate parameters. In contrast, bevacizumab has no significant impact on the patient-related secondary outcomes of OS or QoL, which indicate a direct patient benefit. For this reason, the clinical value of bevacizumab for metastatic breast cancer remains controversial.

Toxicity of pyrethroids and repellency of diethyltoluamide in two deltamethrin-resistant colonies of Triatoma infestans Klug, 1834 (Hemiptera: Reduviidae)

The aim of the currrent investigation was to evaluate (a) the toxicity of three pyrethroids (deltamethrin, lambda-cyhalothrin, and tetramethrin); (b) the effect of these insecticides on the locomotor activity; and (c) the repellent effect of N,N-diethyl-m-toluamide (DEET) on two deltamethrin-resistant strains of Triatoma infestans from Argentina (El Chorro and La Toma), and one susceptible strain. The resistance ratios (RRs) obtained for the La Toma strain were: > 10,769, 50.7, and > 5.2 for deltamethrin, lambda-cyhalothrin, and tetramethrin respectively. The RRs for the El Chorro strain were: > 10,769, 85.8, and > 5.2 for deltamethrin, lambda-cyhalothrin, and tetramethrin respectively. The hyperactivity usually caused by the three pyrethroids was in both the deltamethrin-resistant strains compared to the susceptible reference strain. No differences were observed in the repellent effect of DEET between the three groups. These results indicate that the deltamethrin-resistant insects have a cross resistance to lambda-cyhalothrin and tetramethrin, and are also resistant to the first symptom of pyrethroid poisoning (hyperactivity). However, the sensorial process related to DEET repellency does not appear to be altered.

Patterns of hepatitis B virus infection in Brazilian human immunodeficiency virus infected patients: high prevalence of occult infection and low frequency of lamivudine resistant mutations

Hepatitis B virus (HBV) molecular profiles were determined for 44 patients who were infected with human immunodeficiency virus (HIV) type 1 and had antibodies to the hepatitis B core antigen (anti-HBc), with and without other HBV serological markers. In this population, 70% of the patients were under lamivudine treatment as a component of antiretroviral therapy. HBV DNA was detected in 14 (32%) patients. Eight out of 12 (67%) HBsAg positive samples, 3/10 (30%) anti-HBc only samples, and 3/22 (14%) anti-HBs positive samples were HBV DNA positive. HBV DNA loads, measured by real time polymerase chain reaction, were much higher in the HBsAg positive patients (mean, 2.5 × 10(9) copies/ml) than in the negative ones (HBV occult infection; mean, 2.7 × 10(5) copies/ml). Nine out of the 14 HBV DNA positive patients were under lamivudine treatment. Lamivudine resistant mutations in the polymerase gene were detected in only three patients, all of them belonging to the subgroup of five HBsAg positive, HBV DNA positive patients. A low mean HBV load (2.7 × 10(5) copies/ml) and an absence of lamivudine resistant mutations were observed among the cases of HBV occult infection.

Identification and molecular characterization of Van A-type vancomycin-resistant Enterococcus faecalis in Northeast of Brazil

The isolation of vancomycin resistant enterococci (VRE) in Brazil has rapidly increased, following the world wide tendency. We report in the present study the first isolation of vancomycin resistant Enterococcus faecalis (VRE) in the Northeast of Brazil. The four VRE isolates were characterized for antimicrobial susceptibility, genotypic typing by macro restriction of chromosomal DNA followed by pulsed-field gel electrophoresis and for characterization of the Tn1546-like element and plasmid contents. The isolates showed resistance to multiple antibiotics and a single genotype profile, suggesting the dissemination of a single clone among the patients. Tn1546 associated to genetic elements as plasmids shows the importance of infection control measures to avoid the spreading of glycopetide resistance by conjugative transfer of VanA elements.

Management of a post-operative multi-resistant infectious spondylitis associated with a kyphotic deformity.

Anterior spinal infection (prevertebral abscess and/or discitis) after posterior instrumentation for vertebral fractures is a challenging complication, since a new implant may become necessary anteriorly, in a septic environment. Generally accepted management guidelines are yet to be established. The authors present a case of posterior instrumentation for fractures of T12 and L1, complicated after 9 months with an anterior infection (prevertebral abscess and discitis) with extended-spectrum beta-lactamase (ESBL) producing Escherichia coli (E. coli). This case is unique in that the multi-resistant organism was isolated only after the second stage of infection treatment, which consisted of anterior débridement and anterior implantation of titanium cages and rods. In this particular case, infection was controlled despite implantation of multiple cages, screws and rods, and fusion was achieved, by means of intravenous antibiotic treatment for 12 months. At the latest follow-up, 24 months post surgery, there was no evidence of infection. This problem case may be helpful for surgeons confronted with spinal deformities secondary to infections with multi-resistant organisms.

Differential lectin labelling of circulating hemocytes from Biomphalaria glabrata and Biomphalaria tenagophila resistant or susceptible to Schistosoma mansoni infection

Lectins/carbohydrate binding can be involved in the Schistosoma mansoni recognition and activation of the Biomphalaria hemocytes. Therefore, expression of lectin ligands on Biomphalaria hemocytes would be associated with snail resistance against S. mansoni infection. To test this hypothesis, circulating hemocytes were isolated from B. glabrata BH (snail strain highy susceptible to S. mansoni), B. tenagophila Cabo Frio (moderate susceptibility), and B. tenagophila Taim (completely resistant strains), labelled with FITC conjugated lectins (ConA, PNA, SBA, and WGA) and analyzed under fluorescence microscopy. The results demonstrated that although lectin-labelled hemocytes were detected in hemolymph of all snail species tested, circulating hemocytes from both strains of B. tenagophila showed a larger number of lectin-labelled cells than B. glabrata. Moreover, most of circulating hemocytes of B. tenagophila were intensively labelled by lectins PNA-FITC and WGA-FITC, while in B. glabrata small hemocytes were labeled mainly by ConA. Upon S. mansoni infection, lectin-labelled hemocytes almost disappeared from the hemolymph of Taim and accumulated in B. glabrata BH. The role of lectins/carbohydrate binding in resistance of B. tengophila infection to S. mansoni is still not fully understood, but the data suggest that there may be a correlation to its presence with susceptibility or resistance to the parasite.

Biomphalaria tenagophila: dynamics of populations of resistant and susceptible strains to Schistosoma mansoni, with or without pressure of the parasite

Resistant (Taim, RS) and susceptible albino (Joinville, SC) Biomphalaria tenagophila populations were kept together, at different proportions, throughout a 18-month-period. Some of the snail groups were submitted to Schistosoma mansoni infection. The targets of this study were (a) to analyze the populational dynamics among resistant and susceptible individuals to S. mansoni; (b) to study the resistance phenotype in descendants of cross-breeding; (c) to observe whether the parasite could exert any kind of selection in those snail populations. Throughout the experiment it could be observed that the susceptible B. tenagophila strain (Joinville) underwent a selective pressure of the parasite that was negative, since the individuals showed a high mortality rate. Although B. tenagophila (Taim) population presented a higher mortality rate without pressure of the parasite, this event was compensated by a reproductive capacity. B. tenagophila Taim was more fecund than B. tenagophila Joinville and was able to transmit the resistance character to their descendants. F1 generation obtained by cross-breeding between resistant and susceptible lineages was completely resistant to S. mansoni infection, irrespective of the Taim proportion. Moreover, less than 5% of F2 progeny were susceptible to S. mansoni infection.

Multi-drug resistant (MDR) bacteria - including accessible formats

Information for patients and visitors on MDR bacteria and how to help prevent the spread of infection.Accessible formatsThe below document is available as a pdf and in accessible formats.�Accessible formats are alternatives to printed information, used by people who are blind or visually impaired. These accessible formats include HTML, audio and braille. �For audio and HTML copies please click on the links below. For braille copies please contact Caroline McGeary on 0300 555 0114.

Extended spectrum beta lactamase (ESBL) resistant bacteria - including accessible formats

Information for patients and visitors on extended spectrum beta lactamase (ESBL) resistant bacteria and how to help prevent the spread of infection.Accessible formatsThe below document is available as a pdf and in accessible formats. Accessible formats are alternatives to printed information, used by people who are blind or visually impaired. These accessible formats include HTML, audio and braille. �For audio and HTML copies please click on the links below. For braille copies please contact Caroline McGeary on 0300 555 0114.

Characterization of ndh gene of isoniazid resistant and susceptible Mycobacterium tuberculosis isolates from Brazil

Resistance in Mycobacterium tuberculosis to isoniazid (INH) is caused by mutations in the catalase-peroxidase gene (katG) , and within the inhA promoter and/or in structural gene. A small percentage (~ 10%) of INH-resistant strains do not present mutations in both of these loci. Other genes have been associated with INH resistance including the gene encoding for NADH dehydrogenase (ndh) . Here we report the detection of two ndh locus mutations (CGT to TGT change in codon 13 and GTG to GCG change in codon 18) by analyzing 23 INH-resistant and in none of 13 susceptible isolates from Brazilian tuberculosis patients. We also detected two isolates without a mutation in ndh, or any of the other INH resistance-associated loci examined, suggesting the existence of additional, as yet to be described, INH resistance mechanisms.

The presence of qacA/B gene in Brazilian methicillin-resistant Staphylococcus aureus

A total of 74 methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from three government hospitals in 2002 and 2003 were examined concerning the distribution of qacA/B gene, which is the determinant of resistance to quaternary ammonium compounds largely employed in hospital disinfection. By polymerase chain reaction the qacA/B gene was found in 80% of the isolates, which is a significant result considering it is the first time that qacA/B gene is being reported for Brazilian MRSA strains and it is presented at a high rate.

Transferrin uptake may occur through detergent-resistant membrane domains at the cytopharynx of Trypanosoma cruzi epimastigote forms

Uptake of transferrin by epimastigote forms of the protozoan Trypanosoma cruzi occurs mainly through a cytostome/ cytopharynx, via uncoated endocytic vesicles that bud off from the bottom of the cytopharynx. We have here examined whether detergent-resistant membrane (DRM) domains might be involved in this process. Purified whole cell membrane fractions were assayed for cholesterol levels and used in dot blot analyses. Detergent-resistant membrane markers (cholera B toxin and anti-flotillin-1 antibody) presented positive reaction by dot blots in cholesterol-rich/ protein-poor membrane sub-fractions. The positive dot blot fraction was submitted to lipid composition analysis, showing composition similar to that of raft fractions described for other eukaryotic cells. Immunofluorescence assays allowed the localization of punctual positive signal for flotillin-1, matching the precise cytostome/ cytopharynx location. These data were confirmed by immunofluorescence assays with the co-localization of flotillin-1 and the transferrin uptake site. Our data suggest that DRM domains occur and are integrated at the cytostome/ cytopharynx of T. cruzi epimastigotes, being the main route for transferrin uptake.