Cystitis is a common infection. The alarmingly high resistance rates exhibited by contemporary uropathogens necessitate the re-evaluation of old antibiotics.

To evaluate the effectiveness and safety of fosfomycin compared with other antibiotics for the treatment of patients with cystitis.

We performed a meta-analysis of randomized controlled trials (RCTs), generated from searches performed in PubMed, Scopus and Cochrane CENTRAL, which involved patients with cystitis treated with fosfomycin versus other antibiotics.

Twenty-seven trials (eight double-blind) were included. Sixteen of these 27 trials involved exclusively non-pregnant female patients, 3 involved adult mixed populations of older age, 5 involved pregnant patients and 3 involved paediatric patients. Regarding clinical success, no difference was found in the comprehensive analysis regarding all comparators combined [10 RCTs, 1657 patients, risk ratio (RR) = 1.00, 95% confidence interval (CI) = 0.98–1.03] in trials involving non-pregnant females and in trials involving mixed populations. Insufficient relevant data were provided from trials involving paediatric and pregnant patients. No difference between fosfomycin and comparators was also found in all comparisons regarding the remaining effectiveness outcomes (namely microbiological success/relapse/re-infection). Fosfomycin had a comparable safety profile with the evaluated comparators in non-pregnant women, mixed and paediatric populations, whereas it was associated with significantly fewer adverse events in pregnant women (4 RCTs, 507 patients, RR = 0.35, 95% CI = 0.12–0.97).

In the era of high drug resistance rates, reported even among community-acquired uropathogens, fosfomycin may provide a valuable alternative option for the treatment of cystitis in non-pregnant and pregnant women and in elderly and paediatric patients.

To compare lipid profiles in HIV-infected adults receiving atazanavir-based regimens.

We conducted a systematic review of randomized controlled trials (RCTs) comparing atazanavir or atazanavir/ritonavir with a comparator and evaluated lipids at 48 weeks. We searched MEDLINE, EMBASE, CENTRAL, LILACS, Current Controlled Trials, National Institutes of Health Clinical Trials Registry, trials at AIDSinfo and HIV conference proceedings to May 2009. Standardized mean difference (SMD) between study arms in change from baseline to week 48 in lipid parameters was determined weighted by study size and 95% confidence intervals (CI) were calculated.

Nine eligible RCTs were identified (n = 3346). SMDs (mmol/L) in four RCTs comparing atazanavir/ritonavir with a ritonavir-boosted protease inhibitor were: total cholesterol, –0.62 (95% CI –0.72, –0.51); low-density lipoprotein (LDL) cholesterol, –0.31 (95% CI –0.44, –0.17); high-density lipoprotein (HDL) cholesterol, –0.16 (95% CI –0.27, –0.06); non-HDL cholesterol, –0.58 (95% CI –0.69, –0.48); and triglycerides, –0.46 (95% CI –0.58, –0.34). Atazanavir compared with non-atazanavir (three RCTs) found lower total, LDL and non-HDL cholesterol, and triglycerides [SMD –0.87 mmol/L (95% CI –0.99, –0.76); –0.56 mmol/L (95% CI –0.67, –0.45); –0.88 mmol/L (95% CI –0.99, –0.76); and –0.56 mmol/L (95% CI –0.75, –0.36), respectively], but HDL cholesterol did not differ [–0.16 mmol/L (95% CI –0.49, 0.16)]. In the atazanavir/ritonavir versus atazanavir comparison (two RCTs), total [SMD 0.44 mmol/L (95% CI 0.23, 0.65)] and non-HDL cholesterol [SMD 0.44 mmol/L (95% CI 0.23, 0.65)] were higher, but HDL cholesterol, LDL cholesterol and triglycerides were not different.

At 48 weeks, plasma lipid concentrations were lower with atazanavir/ritonavir than with other ritonavir-boosted protease inhibitor regimens. Total and non-HDL cholesterol were higher with atazanavir/ritonavir than atazanavir alone.

Efavirenz is extensively metabolized by CYP2B6, and associations between CYP2B6 polymorphisms and plasma efavirenz exposure have been reported. The objective of this study was to investigate CYP2B6 haplotype structure and functional consequences in a Latin American population.

Two hundred and nineteen patients were recruited at Fundación Arriarán, Chile, between September and December 2008. Plasma efavirenz concentrations were determined using liquid chromatography with mass spectrometry. Genotyping for 30 single nucleotide polymorphisms (SNPs) with a minor allele frequency of >0.05 in the HapMap CEU population at intervals of ~1 kb across the CYP2B6 locus was conducted using Sequenom iPLEX MALDI-TOF.

Thirteen SNPs passed quality control and, of these, statistically significant associations (P < 0.001) with plasma efavirenz concentrations were observed for 11. Pairwise tagging SNP analysis (R² > 0.8) identified 3 SNPs (rs10403955, rs2279345 and rs8192719) representative of the 11 associated SNPs. A composite genetic model of these three alleles was constructed, and an association between carriers of four to six of these alleles and the risk of efavirenz plasma concentrations >4 µg/mL was identified with an odds ratio of 48.1 (95% confidence interval: 13.5–207.7). This represents a positive predictive value of 80.9% and a negative predictive value of 91.8%, with sensitivity of 57.9% and specificity of 97.2%.

A composite genetic model of CYP2B6 SNPs in a Chilean HIV-positive cohort may have value in predicting concentrations of efavirenz associated with a higher likelihood of CNS toxicity. Further investigation of the functional basis of these associations is now required.

To determine the genetic composition of the first VanA-type plasmid (pIP816) reported, which was isolated from a clinical Enterococcus faecium (BM4147) strain in France in 1986, and to reveal the genetic units responsible for the dissemination of the vanA gene cluster by comparisons with current, published and additionally generated vanA-spanning plasmid sequences obtained from a heterogeneous E. faecium strain collection (n = 28).

Plasmid sequences were produced by shotgun sequencing using ABI dye chemistry and primer walking, and were subsequently annotated. Comparative sequence analysis of the vanA region was done with published plasmids, with a partial vanA plasmid (pVEF4) reported here and to >140 kb of sequence obtained from a collection of vanA-harbouring plasmid fragments.

Bioinformatic analyses revealed that pIP816 from 1986 and contemporary vanA plasmids shared a conserved genetic fragment of 25 kb, spanning the 10.85 kb vanA cluster encoded by Tn1546, and that the larger unit is present in both clinical and animal complexes of E. faecium. A new group II intron in pVEF4 was characterized.

Comparative DNA analyses suggest that Tn1546 disseminates in and between clonal complexes of E. faecium as part of a larger genetic unit, possibly as a composite transposon flanked by IS1216 elements.

To analyse Streptococcus agalactiae (group B Streptococcus; GBS) isolates collected in Poland from various human infections and carriage in respect of their clonality, distribution of virulence factors and antimicrobial resistance determinants, including the detection of transposons involved in the dissemination of antimicrobial resistance.

One hundred and fourteen GBS isolates were analysed by multilocus sequence typing (MLST), serotyping and detection of alp genes of the -like-protein (Alp) family. Determinants of resistance to macrolides and tetracycline, and associated transposons, were detected by PCR and analysed by sequencing.

GBS isolates represented 30 different sequence types (STs), grouped in four clonal complexes (CCs), and belonged to seven serotypes. Serotype III was predominant (36.0%), followed by Ia, V, Ib, II, IV and VI. The most common alp genes were rib (26.3%) and alp1/alp5 (23.7%). The bac gene encoding the β-compound of the surface C-protein was present in 17.5% of isolates. Erythromycin resistance (18.4% of isolates) was found in all CCs, but was associated with serotype V and ST1. The most prevalent determinant of resistance was erm(B), usually located on the Tn3872-like transposon. Several changes were observed in the regulatory region of erm(B), some of them resulting in elevated ketolide MICs. Resistance to tetracycline was ubiquitous (91.2%) and its most common determinant was tet(M), occurring in several variants that were typically carried on Tn916-family transposons.

Analysis of bacterial serotypes, alp genes and antimicrobial resistance determinants in the background of MLST-based population structure strengthened evidence of the importance of horizontal gene transfer in GBS evolution.

Multidrug-resistant Acinetobacter strain HK302 was isolated from an outbreak of nosocomial infections in Switzerland in 1977. The aim of the present study was to assess whether this archive strain belongs to one of the known international clonal lineages of Acinetobacter baumannii and whether it harbours a genomic structure related to the AbaR1-like resistance islands.

Multilocus sequence typing (MLST) and HindIII ribotyping were used to determine the taxonomic position of HK302 at the species and subspecies (clonal) levels. The position and structure of the putative resistance island were investigated by AbaR1-based PCR mapping followed by restriction analysis and partial sequencing of amplicons. A. baumannii AYE harbouring AbaR1 was used as a positive control for PCR mapping.

The MLST allelic profile (1-1-1-1-5-1-1) and HindIII ribotype of HK302 were typical of A. baumannii European (EU) clone I. In addition, an AbaR1-related region inserted into the ATPase gene at the same position as AbaR1 was found in HK302. PCR mapping and partial sequencing revealed that this region is structurally congruent with AbaR3, a 63.4 kb island described in an A. baumannii isolate from 2004.

A. baumannii HK302 belongs to EU clone I and harbours an AbaR3-like island related to resistance islands described in EU clone I strains. Our findings suggest that variants of these sophisticated genomic structures already existed in A. baumannii in the late 1970s.

Acinetobacter baumannii has emerged as an important nosocomial pathogen in hospitalized patients, and causes a multitude of infections with significant morbidity and mortality. The aim of this study was to elucidate the role of a novel efflux pump in A. baumannii.

The open reading frame ABAYE1518, annotated as a putative Methyl Viologen resistance protein in the genome of strain A. baumannii AYE, exhibits >50% similarity with members of the major facilitator superfamily (MFS) multidrug efflux pumps. The antimicrobial susceptibility profiles of Escherichia coli KAM32 cells carrying the putative efflux pump were monitored by broth dilution method. Different efflux pump inhibitors were used for fluorimetric efflux assays. The functions of the putative efflux pump were confirmed in A. baumannii by insertional inactivation and complementation. Its expression in clinical isolates was analysed by reverse transcriptase–PCR.

E. coli cells carrying the pump had decreased susceptibility to some antibiotics, disinfectants, dyes and detergents, with enhanced efflux activity. The pump was inactivated in a clinical isolate of A. baumannii AC0037 and further characterization confirmed its role in antimicrobial resistance by active efflux. We found increased expression of the pump in clinical isolates that also exhibited elevated tolerance to antibacterial agents.

This report describes the functions of a novel resistance determinant, a member of the MFS efflux pumps, for the first time in A. baumannii.