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Objective: To compare the short-term effectiveness of ceftriaxone single dose followed by cefixime with a standard treatment of acute uncomplicated pyelonephritis in women. Methods: An open, prospective, and randomised trial [...]

Position and velocity data are analyzed from a release of surface ocean drifters in the Arctic Ocean's Beaufort Sea in ice‐free conditions. Position information is returned at sufficiently high frequency to allow for the investigation of surface‐ocean flows ranging from around 0.5 km in lateral scale (submesoscale, SM, flows) to flows that are tens of kilometers in horizontal extent. Lagrangian statistics from the drifter release are analyzed in conjunction with Eulerian (ship‐based) measurements of surface ocean temperature and salinity. Results show dynamics that are largely consistent with flows at similar scales in the midlatitude oceans. Horizontal wavenumber kspectra of density in the surface ocean scale as k−2, consistent with energetic SM flows. Lagrangian drifters indicate localdispersion in the surface ocean layer at horizontal scales smaller than 10 km, which confirms the presence of active submesoscale dynamics. Features at these scales give rise to lateral diffusivities (in the range 1–103m2s−1) of similar range to values inferred in the midlatitudes. Velocity structure functions present an energy‐cascade inertial range at submesoscales with indication of a transition to a forward energy cascade at scales smaller than 1 km confirming the transition to 3‐D turbulence. The active SM flow‐field drives enhanced lateral and vertical fluxes in the Arctic Ocean mixed layer, which has first‐order implications to the transport of heat, sea‐ice floes, nutrients, and contaminants. Transport and distribution of pollutants and biogechemical tracers is driven by currents in the upper ocean. Surface‐ocean observations in the midlatitudes, as well as numerical modeling, have shown that small‐scale flows (i.e., submesoscale flows) play a key role in this transport. Here we present results from a drifter release experiment in the Arctic Ocean's Beaufort Sea. Results provide in‐situ observational evidence, for the first time, for the presence of submesoscale flows in the Beaufort Sea. These results extend observations of submesoscale flows in the midlatitude oceans, and improve understanding of the Arctic Ocean system where the transport and distribution by submesoscale flows of ocean heat and sea‐ice floes are of climate significance. Surface drifters provide observational evidence for submesoscale flows in the Beaufort SeaSubmesoscale flow features in the mixed‐layer drive drifter separation and lateral transportDispersion of drifters is consistent with the presence of a forward‐cascade inertial range

ABSTRACTAim: The major concern of linezolid is the adverse events. High linezolid trough serum concentration (Cmin) has been associated with toxicity. The aim of this study was to analyze factors associated with high Cmin.Methods: Main clinical characteristics of 104 patients treated with 600 mg/12 hours of linezolid were retrospectively reviewed. Samples were obtained just before the next dose after at least three doses and within the first 8 days of treatment. High Cminwas considered when it was >8 mg/L. Univariate and multivariate analysis were performed.Results: 34.6% patients had a Cmin>8 mg/L, and they were older and had more frequently an estimated glomerular filtration by MDRD <40 mL/min. There were more patients co-treated with rifampin in the group with low Cmin. The only factor independently associated with Cmin>8 was the renal function. Patients with an eGF < 40 mL/min had significantly higher Cminthan those with eGF > 80 mL/min (OR: 4.273) and there was a trend towards a high Cminin patients with eGF between 40-80 mL/min (OR: 2.109).Conclusions: High Cminwere frequent, especially in patients with MDRD <40 mL/min. Therapeutic drug monitoring could be useful to avoid toxicity in patients with renal dysfunction.

ABSTRACTEvidence supporting the combination of aminoglycosides with β-lactams for Gram-negative bacteremia is inconclusive. We have explored the influence on survival of empirical therapy with a β-lactam alone versus that with a β-lactam-aminoglycoside combination by retrospectively analyzing a series of bacteremic episodes due to aerobic or facultative Gram-negative microorganisms treated with single or combination therapy. The outcome variable was a 30-day mortality. Prognostic factors were selected by regression logistic analysis. A total of 4,863 episodes were assessed, of which 678 (14%) received combination therapy and 467 (10%) were fatal. Factors independently associated with mortality included age greater than 65 (odds ratio [OR], 2; 95% confidence interval [CI], 1.6 to 2.6), hospital acquisition (OR, 1.5; 95% CI, 1.2 to 1.9), a rapidly or ultimately fatal underlying disease (OR, 2.5; 95% CI, 2 to 3.2), cirrhosis (OR, 1.9; 95% CI, 1.4 to 2.6), prior corticosteroids (OR, 1.5; 95% CI, 1.1 to 2), shock on presentation (OR, 8.8; 95% CI, 7 to 11), pneumonia (OR, 2.8; 95% CI, 1.9 to 4), and inappropriate empirical therapy (OR, 1.8; 95% CI, 1.3 to 2.5). Subgroup analysis revealed that combination therapy was an independent protective factor in episodes presenting shock (OR, 0.6; 95% CI, 0.4 to 0.9) or neutropenia (OR, 0.5; 95% CI, 0.3 to 0.9). Combination therapy improved the appropriateness of empirical therapy in episodes due to extended-spectrum β-lactamase (ESBL)- or AmpC-producing Enterobacteriaceaeand Pseudomonas aeruginosa. In patients with Gram-negative bacteremia, we could not find an overall association between empirical β-lactam-aminoglycoside combination therapy and prognosis. However, a survival advantage cannot be discarded for episodes presenting shock or neutropenia, hence in these situations the use of combination therapy may still be justified. Combination therapy also should be considered for patients at risk of being infected with resistant organisms, if only to increase the appropriateness of empirical therapy.

Background: Glucose non-fermentative Gram-negative bacilli other than P. aeruginosa (NF) are emerging pathogens.
Aim: To evaluate the epidemiology, clinical characteristics, predictors of acquisition, and outcome of bacteraemia due to NF.
Design: Retrospective analysis of prospectively recorded data.
Methods: We reviewed episodes of NF bacteraemia in patients older than 14 years, recorded through a blood culture surveillance program. Patients were identified at the time of their bacteraemia and prospectively followed.
Results: Between January 1991 and December 2000, 296 episodes of NF bacteraemia were detected: 87% were due to Acinetobacter sp., Pseudomonas sp. other than P. aeruginosa, or Stenotrophomonas maltophilia. The global incidence (0.87 cases per 1000 discharges) remained stable during the study period. Patients were of all ages and both sexes, and 282/296 (95.3%) had some predisposing underlying disease or condition, the most common being haematological malignancies without transplantation (85/296, 28.7%), treatment with steroids (78/296, 26.3%), and transplantation (bone marrow or solid organ) (70/296, 23.6%). Fifty (16.9%) were neutropenic. The most common sources of bacteraemia were central venous catheter infection (117/296, 39.5%) and unknown primary site (97/296, 32.8%). Sixty-one episodes (20.6%) were community-acquired and 235 (79.4%) were nosocomial. Forty-three patients (14.5%) died. Pneumonia (RR 1.5, 95%CI 1.1-14.2), age&lt;65 (RR 3.1, 95%CI 1.4-10.3), hospitalization in the intensive care unit (ICU) (RR 3.2, 95%CI 1.3-9.8), rapidly fatal disease (RR 4.9, 95%CI 3.1-12.6), and severe sepsis (RR 9.8, 95%CI 1.6-19.7) were independent predictors of death. Factors predicting the probability that an episode of nosocomial bacteraemia was due to NF included: rapidly fatal disease (RR 1.23, 95%CI 1.02-4.1), age&lt;65 (RR 2.05, 95%CI 1.4-3), hospitalization in the ICU (RR 2.06, 95%CI 1.4-3, and pneumonia (RR 2.1, 95%CI 1.05-4.8).
Discussion: NF bacteraemia mainly affects patients with malignant haematological disease, with and without transplantation, and patients in the ICU. The most common known source is a central venous catheter, though many sources are unknown. Mortality is relatively low, and depends on the severity of the underlying disease.

Although prostatitis is a common problem the diagnosis is still controversial despite the availability of a wide variety of diagnostic tools. In fact, there is still no accurate method of localizing the infected tissue. The aims of the present study were to assess whether 111In labelled leukocytes (ILLs) accumulated in the infected tissue of acute prostatitis and if such uptake responded to treatment. We prospectively studied 10 adult male patients who had community acquired prostatitis and compared them with six male patients who had urinary tract infections but without prostatitis. An initial urinary culture and two blood cultures were carried out for each patient. All patients were followed up for 8 weeks after therapy was completed. Pre- and post-treatment scintigraphies were performed. Before treatment, all patients with prostatitis showed uptake of ILLs in the prostate area. After the patients had completed treatment with antibiotics, the scintigraphy results showed no uptake in the prostate area in 910 patients. The remaining patient showed a marked decrease in the uptake of ILLs. None of the six patients with urinary tract infection showed ILL uptake in the prostate region. It is suggested that ILLs could be useful for detecting acute prostatitis, especially in clinically ambiguous patients with urological infections. Furthermore, scintigraphy with 111In labelled leukocytes could help to determine the most appropriate course of therapy.

Abstract:  A prospective analysis of 43 episodes of Pseudomonas aeruginosa bacteremia in HIV-1-infected subjects was performed and the results compared with the incidence and outcome of Pseudomonas aeruginosa bacteremia in other high-risk patients, such as transplant recipients, leukemia patients, or patients hospitalized in the intensive care unit. The incidence of bacteremia/fungemia as a whole and of gram-negative and Pseudomonas aeruginosa bacteremia in particular was greater in HIV-1-infected subjects than in the unselected general population admitted. In contrast, the incidence of Pseudomonas aeruginosa bacteremia in HIV-1-infected patients did not differ from that in patients with other high-risk conditions. In patients with HIV-1 infection, independent risk factors for presenting Pseudomonas aeruginosa bacteremia were nosocomial origin (OR, 2.7; 95% CI, 1.3–5.7), neutropenia (OR, 2.7; 95% CI, 1.07–6.8), previous treatment with cephalosporins (OR, 3.6; 95% CI, 1.1–11.6), and a CD4+ cell count lower than 50 cells/mm3 (OR, 3.1; 95% CI, 1.7–8.6). Primary bacteremia and pneumonia were the most common forms of presentation. Fourteen (33%) patients died as a consequence of the bacteremia. The presence of severe sepsis (OR, 17.5; 95% CI, 3.2–68) and the institution of inappropriate definitive antibiotic therapy (OR, 2.7; 95% CI, 1.1–13) were independently associated with a poor outcome. One year after the development of bacteremia, only eight (19%) patients remained alive.

ABSTRACTWe determined the linezolid concentrations in serum samples and aqueous humors (AHs) from 21 patients undergoing cataract extraction. Cataract removal was performed at various times (from 60 to 270 min) after the end of a 30-min infusion of 600 mg of linezolid. Serum samples were obtained 1 h after the end of linezolid administration to determine the maximum concentration of linezolid (Cmax); AHs and a second serum sample were taken simultaneously during the operation, and the concentrations of linezolid in AH (CAH) and serum (CS) were determined. The mean CAH1 h after linezolid administration was 4.94 μg/ml, and the mean ratio of CAHto CS(R= CAH/CS) was 0.43. All patients had a CAHof >2 μg/ml, which was higher than the MIC at which 90% of Staphylococcus epidermidisstrains are inhibited.

ABSTRACTThe antibiotic linezolid is a ribosomal inhibitor with excellent efficacy. Although the administration period has been reduced to 28 days, side effects, usually of hematologic or neuropathic origin, are still reported due to secondary inhibition of mitochondrial protein synthesis. Susceptibility to linezolid toxicity remains unknown. Therefore, the objective of this study was to gain an understanding of clinical heterogeneity in response to identical linezolid exposures through exhaustive examination of the molecular basis of tissue-dependent mitotoxicity, consequent cell dysfunction, and the association of mitochondrial genetics with adverse effects of linezolid administered for the recommended period. Peripheral blood mononuclear cells (PBMC) and skin nerve fibers from 19 and 6 patients, respectively, were evaluated before and after a 28-day linezolid treatment in order to assess toxic effects on mitochondria and cells. Mitochondrial DNA haplotypes and single nucleotide polymorphisms (SNPs) in ribosomal sequences where linezolid binds to mitochondrial ribosomes were also analyzed to investigate their genetic contributions. We found that linezolid reduced mitochondrial protein levels, complex IV activity, and mitochondrial mass in PBMC and was associated with a trend toward an increase in the rate of apoptosis. In skin tissue, mitochondrial mass increased within nerve fibers, accompanied by subclinical axonal swelling. Mitochondrial haplogroup U, mutations in 12S rRNA, and the m.2706A→G, m.3197T→C, and m.3010G→A polymorphisms in 16S rRNA showed a trend toward an association with increased mitochondrial and clinical adverse effects. We conclude that even when linezolid is administered for a shorter time than formerly, adverse effects are reported by 63% of patients. Linezolid exerts tissue-dependent mitotoxicity that is responsible for downstream cellular consequences (blood cell death and nerve fiber swelling), leading to adverse hematologic and peripheral nervous side effects. Multicentric studies should confirm genetic susceptibility in larger cohorts.

ABSTRACTThe use of radiopharmaceuticals for the diagnosis of infection is increasing due to their ability to distinguish between septic and aseptic inflammation. The aim of this study was to analyze the intracellular accumulation of technetium-99m-ciprofloxacin in strains of Staphylococcus aureusand Pseudomonas aeruginosaharboring an overexpression of NorA and MexAB-OprM, respectively.

A case ofCandida albicansendocarditis is described which developed in a heroin addict with aortic valvulopathy after an episode of cutaneous and chondrocostal candidiasis related to the use of “brown” heroin. To our knowledge this is the first case reported in the English literature. This complication should be suspected in all heroin addicts with this new syndrome, especially if valvulopathy is present.

Five hundred forty-three episodes of nosocomial bacteremia were prospectively followed in a large Spanish university hospital. The commonest isolates were Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida species. The most frequent sources of infection were intravenous lines, urinary tract, and lower respiratory tract. Overall mortality was 18%. A step-forward logistic regression analysis defined eight variables independently influencing the outcome: shock, underlying rapidly fatal disease, high-risk source of bacteremia (intraabdominal, lower respiratory tract, or not identified), age more than 70 years, hospitalization in intensive care or medical units, inappropriate antibiotic treatment, infection due to a high-risk microorganism (P. aeruginosa, Serratia marcescens, Klebsiella, Bacteroides, or Candida), and development of septic metastasis. The identification of those factors independently influencing the outcome and their possible modification may represent a further step in the control of nosocomial bacteremia by improving its prognosis.