Haematological and acute-phase response of dogs with experimental skin <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> infection to treatment with antibiotic and parthenolide

Changes in white blood cells, leukogram patterns, the positive acute-phase protein (APP) fibrinogen and negative APPs (albumin and arylesterase) were monitored to evaluate their potential as sensitive indicators throughout the course of therapy in canine skin Pseudomonas aeruginosa infection. The study was performed on 15 male mixed-breed dogs, divided in three groups of 5 dogs each. Dogs from group A were injected subcutaneously with P. aeruginosa bacterial culture (1?×?10⁸ CFU/mL) at a dose of 0.3 mL/kg and treated with enrofloxacin (5 mg/kg, s.c.) on post infection hour 48 for 10 consecutive days. Dogs from group B were infected and treated with a combination of enrofloxacin (at above-mentioned dose and intervals) and parthenolide (feverfew extract 90 mg, 0.7 % parthenolide). The schedule consisted of daily oral intake of two capsules of feverfew beginning on post infection hour 4 and continued for 6 days. The control group C included healthy dogs, injected s.c. with 0.3 mL/kg physiological saline. The haematological indices and APPs were assayed before infection and on 4th, 24th, 48th and 72nd hours and on 7th, 10th and 14th days after infection. Infected and antibiotic-treated dogs responded with significant leukocytosis, left shift, eosinopaenia and lymphopaenia between hours 24 and 72. In this group, fibrinogen increased substantially by post infection hours 24 (p?<?0.01 vs 0 h; p?<?0.05 vs group C), 48 (p?<?0.001 vs 0 h; p?<?0.05 vs group C) and 72 (p?<?0.001 vs 0 h; p?<?0.01 vs group C) while albumin reduction was marked by hours 48 (p?<?0.05 vs 0 h) and 72 (p?<?0.05 vs 0 h; p?<?0.001 vs group C) and day 7 (p?<?0.01 vs 0 h; p?<?0.001 vs group C). The combination of enrofloxacin and parthenolide modified, at a significant extent, the deviations in studied parameters except for eosinophil percentage, which persisted low.     

Gasterophilosis in horses in Sardinia (Italy): effect of meteorological variables on adult egg-laying activity and presence of larvae in the digestive tract,and update of species

Gasterophilus larvae are common obligate parasites of the digestive tract of the equids. Horses become infected with this parasite by ingesting the larvae hatched from eggs laid by the female flies. In this study carried out monthly, we (i) counted the Gasterophilus eggs deposited by female flies on the coat of 30 grazing horses, (ii) counted and identified the Gasterophilus larvae retrieved from the digestive tract of 128 slaughtered horses, and (iii) compared these results to meteorological data. Eggs were deposited on all monitored horses, and were present from October to January and from May to September, whereas they were absent from February to April. The number of laid eggs was significantly different between the months, body regions, genders, and age classes (p?<?0.05). Larvae were recovered in 112 (87.5 %) horses, and 6 species of Gasterophilus were identified. The prevailing species were Gasterophilus intestinalis (recovered in 110 horses; 85.9 %) and Gasterophilus nasalis (69 horses; 53.9 %), recovered in all months. Gasterophilus inermis (5 horses; 3.9 %), Gasterophilus pecorum (3 horses; 2.3 %), Gasterophilus haemorrhoidalis (3 horses; 2.3 %)¸ and Gasterophilus meridionalis (2 horses; 1.6 %) larvae were also found. Significant differences were found among monthly larval burdens for both Gasterophilus spp. and G. intestinalis (p?<?0.05), but not for G. nasalis (p?>?0.05). Larval burdens and prevalences did not differed significantly between both genders and age classes (p?>?0.05). Monthly eggs and larvae trends were not significantly correlated (p?>?0.05). With regard to the meteorological variables, minimum air temperature was significantly correlated with the eggs trend (rho?=?1.000; p?<?0.001) and maximum air temperature with the Gasterophilus spp. (rho?=?0.972; p?<?0.001) and G. intestinalis (rho?=?0.972; p?<?0.001) larvae trends. In addition, the number of hours with a temperature below +10 °C was significantly correlated with G. intestinalis larvae trend (rho?=?0.602; p?<?0.05). Our findings confirmed that in Sardinia, Gasterophilosis is an important parasitosis in the horses, and it needs more attention and extensive and/or correct treatment to reduce its prevalence.     

Behavioral and electrophysiological evidence for attenuation of CNS by aqueous extract from <Emphasis Type="Italic">Citrus aurantium</Emphasis> (CaL) flowers in rat

Anxiety disorders have a relatively high prevalence in most countries. Chemical drugs used to treat anxiety have some unwanted side effects. Therefore, using medicinal plants is useful. Citrus aurantium L. (CaL) flowers are used in Iran to treat anxiety as a folk medicine. We investigated its anxiolytic and sedative effects. We used elevated plus maze and pentobarbital sodium sleeping time tests to evaluate the anxiolytic and sedative effects of CaL flowers on CNS, respectively. In addition, by using extracellular single unit recording technique, we evaluated the depressant action of CaL on neuronal activity of basolateral amygdale (BLA), one of the major structures involved in anxiety. CaL flower aqueous extract (62.5, 125 mg/kg) increased the percentage of time spent in open arms and reduced the percent of time spent in closed arms (p?<?0.05). It also reduced locomotor activity at 250 mg/kg (p?<?0.05). CaL flower aqueous extract (125, 250 mg/kg) prolonged the duration of pentobarbital sleeping time [(p?<?0.05) and (p?<?0.01), respectively] and shortened the onset of sleep in rats (p?<?0.05). CaL reduced the firing rate of BLA neurons (p?<?0.05). Our data suggests that CaL flowers have sedative and anxiolytic effects.     

Intrapulmonary percussive ventilation improves lung function in cystic fibrosis patients chronically colonized with <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis>: a pilot cross-over study

High levels of shear stress can prevent and disrupt Pseudomonas aeruginosa biofilm formation in vitro. Intrapulmonary percussive ventilation (IPV) could be used to introduce shear stress into the lungs of cystic fibrosis (CF) patients to disrupt biofilms in vivo. We performed a first-of-its-kind pilot clinical study to evaluate short-term IPV therapy at medium (200 bursts per minute, bpm) and high frequency (400 bpm) as compared to autogenic drainage (AD) on lung function and the behavior of P. aeruginosa in the CF lung in four patients who are chronically colonized by P. aeruginosa. A significant difference between the three treatment groups was observed for both the forced expiratory volume in 1 s (FEV1) and the forced vital capacity (FVC) (p?<?0.05). More specifically, IPV at high frequency significantly increased FEV1 and FVC compared to AD (p?<?0.05) and IPV at medium frequency (p?<?0.001). IPV at high frequency enhanced the expression levels of P. aeruginosa planktonic marker genes, which was less pronounced with IPV at medium frequency or AD. In conclusion, IPV at high frequency could potentially alter the behavior of P. aeruginosa in the CF lung and improve lung function. Trial registration: The trail was retrospectively registered at the ISRCTN registry on 6 June 2013, under trial registration number ISRCTN75391385.     

Influence of blood flow velocity on arterial distensibility of carotid artery in healthy men

Decreased distensibility of carotid artery is independently associated with the incidence of cardiovascular and cerebrovascular events. Arterial distensibility is determined by vascular tone. Since shear stress is an important driving force of vasodilatory substances production form endothelial cells, we hypothesized that local basal (i.e., resting) arterial blood flow velocity is associated with regional arterial distensibility. To test this hypothesis, we determined the influence of local blood flow velocity on carotid arterial distensibility in cross-sectional study design. In a total of 73 apparent healthy men (18–64 years), carotid arterial properties, including measures of carotid arterial distensibility and BFV at rest, were evaluated via B-mode and Doppler ultrasound imaging and applanation tonometry system. Carotid arterial peak BFV and the absolute and normalized pulsatile BFV significantly correlated with age (r = ?0.453 to ?0.600, p < 0.0001), whereas mean and minimum BFV were not influenced by age. Distensibility coefficient of carotid artery correlated with peak BFV (r = 0.305, p < 0.01) and more strongly with pulsatile (i.e., systolic minus end-diastolic) BFV (r = 0.406, p < 0.0001) and the normalized pulsatile BFV by time-averaged velocity (r = 0.591, p < 0.0001). Multi-regression analysis revealed that age (β = ?0.57, p < 0.0001) was the primary independent determinant for distensibility coefficient. In addition with this, carotid lumen diameter (β = ?0.202, p < 0.01) and the normalized pulsatile BFV (β = 0.237, p < 0.05) were significant independent determinants of distensibility coefficient. Qualitatively similar results (although inverse in direction) were obtained by use of β-stiffness index. These results suggest that greater gradient of blood flow velocity during a cardiac cycle are favorably associated with distensibility of carotid artery.     

<Emphasis Type="Italic">CDKN1A</Emphasis> histone acetylation and gene expression relationship in gastric adenocarcinomas

CDKN1A is a tumor suppressor gene involved in gastric carcinogenesis and is a potential target for histone deacetylase inhibitor-based therapies. Upregulation of CDKN1A is generally observed in several cell lines after histone deacetylase inhibitor treatment; however, little is known about the histone acetylation status associated with this gene in clinical samples, including gastric tumor tissue samples. Therefore, our goal was to quantify the H3K9 and H4K16 acetylation levels associated with three CDKN1A regions in 21 matched pairs of gastric adenocarcinoma and corresponding adjacent non-tumor samples by chromatin immunoprecipitation and to correlate these data with the gene expression. Our results demonstrated that the ?402, ?20, and +182 CDKN1A regions showed a significantly increased acetylation level in at least one of the histones evaluated (p < 0.05, for all comparisons), and these levels were positively correlated in gastric tumors. However, an inverse correlation was detected between both H3K9 and H4K16 acetylation at the ?402 CDKN1A region and mRNA levels in gastric tumors (r = ?0.51, p = 0.02; r = ?0.60, p < 0.01, respectively). Furthermore, increased H4K16 acetylation at the ?20 CDKN1A region was associated with gastric tumors of patients without lymph node metastasis (p = 0.04). These results highlight the complexity of these processes in gastric adenocarcinoma and contribute to a better understanding of CDKN1A regulation in carcinogenesis.     

Prognostic impact of hyperglycemia at onset of methicillin-sensitive <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> bacteraemia

Previous reports have associated hyperglycemia to poor outcome among aged and comorbid Staphylococcus aureus bacteraemia (SAB) patients. However, the prognostic impact of hyperglycemia in SAB irrespective of age and underlying conditions including a diagnosis of diabetes has received little attention. The objective here was to evaluate the prognostic relevance of hyperglycemia at onset of methicillin-sensitive SAB (MS-SAB). It was a retrospective study of MS-SAB patients. Blood glucose was measured within 24 h of positive blood cultures. The patient cohort was analyzed en bloc and by categorization according to age, underlying conditions and a diagnosis of diabetes. Altogether 161 patients were identified. High initial blood glucose levels were observed among diabetics (p?<?0.001), patients with deep infections (p?<?0.05) and poor outcome at 28- or 90-days (p?<?0.05). Receiver operating characteristics presented the glucose cut-off level of 7.2 mmol/L as a significant predictor of mortality with an area under the curve of 0.63 (95% CI 0.52–0.75, p?<?0.05). Blood glucose ≥7.2 mmol/L connected to higher 28- (9 vs. 20%, p?<?0.05) and 90-day (14 vs. 29%, p?<?0.01) mortality. In Cox proportional hazard regression the blood glucose cut-off value of 7.2 mmol/L significantly predicted 90-day mortality (HR, 2.12; 95% CI, 1.01–4.46; p?<?0.05). Among young and healthy non-diabetics the negative prognostic impact of high glucose was further accentuated (HR 7.46, p?<?0.05). High glucose levels had no prognostic impact among diabetics. Hyperglycemia at SAB onset may associate to poor outcome. The negative prognostic impact is accentuated among young and healthy non-diabetics.     

Association between duration of intravenous antibiotic administration and early-life microbiota development in late-preterm infants

Antibiotic treatment is common practice in the neonatal ward for the prevention and treatment of sepsis, which is one of the leading causes of mortality and morbidity in preterm infants. Although the effect of antibiotic treatment on microbiota development is well recognised, little attention has been paid to treatment duration. We studied the effect of short and long intravenous antibiotic administration on intestinal microbiota development in preterm infants. Faecal samples from 15 preterm infants (35?±?1 weeks gestation and 2871?±?260 g birth weight) exposed to no, short (≤ 3 days) or long (≥ 5 days) treatment with amoxicillin/ceftazidime were collected during the first six postnatal weeks. Microbiota composition was determined through 16S rRNA gene sequencing and by quantitative polymerase chain reaction (qPCR). Short and long antibiotic treat ment significantly lowered the abundance of Bifidobacterium right after treatment (p?=?0.027) till postnatal week three (p?=?0.028). Long treatment caused Bifidobacterium abundance to remain decreased till postnatal week six (p?=?0.009). Antibiotic treatment was effective against members of the Enterobacteriaceae family, but allowed Enterococcus to thrive and remain dominant for up to two weeks after antibiotic treatment discontinuation. Community richness and diversity were not affected by antibiotic treatment, but were positively associated with postnatal age (p?<?0.023) and with abundance of Bifidobacterium (p?=?0.003). Intravenous antibiotic administration during the first postnatal week greatly affects the infant’s gastrointestinal microbiota. However, quick antibiotic treatment cessation allows for its recovery. Disturbances in microbiota development caused by short and, more extensively, by long antibiotic treatment could affect healthy development of the infant via interference with maturation of the immune system and gastrointestinal tract.     

Should we expand the indications for the DAIR (debridement,antibiotic therapy,and implant retention) procedure for <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> prosthetic joint infections? A multicenter retrospective study

To evaluate factors associated with failure in patients treated with DAIR (debridement, antibiotic therapy, and implant retention) for Staphylococcus aureus prosthetic joint infections (PJIs). We retrospectively analyzed consecutive patients with stable PJI due to S. aureus treated with DAIR at six hospitals between 2010 and 2014. Cox proportional hazards regression was used to study factors associated with treatment failure at 2 years. Of 154 eligible patients, 137 were included (mean age 73?±?13 years; male 56%). The estimated success rate according to the Kaplan–Meier method was 76.2 [95% CI 68–83] at 2 years of follow-up. In multivariate analysis, longer duration of treatment (hazard ratio (HR) 0.78 [0.69–0.88]; p?<?0.001) and combination therapy including rifampin (HR 0.08 [0.018–0.36]; p?=?0.001) were independently associated with success, whereas active smoking was independently associated with failure (HR 3.6 [1.09–11.84]; p?=?0.036). When the analysis was restricted to patients with early infection onset (<?3 months), early acute infection was also predictive of a better prognosis (HR 0.25 [0.09–0.7]; p?=?0.009). Failure was not associated with time from prosthesis insertion to debridement, nor with duration of symptoms >?3 weeks and type of prosthesis (hip or knee). These results remained unchanged when the 14 patients under immunosuppressive therapy were removed from analysis. These data suggest that DAIR can be performed even if infection and symptoms are delayed but reserved to patients who are able to follow rifampin-based combination therapy for a prolonged duration that should not be different for hip and knee PJI.     

Risk prediction in infective endocarditis by modified MELD-XI score

The suitability of the model for end-stage liver disease excluding international normalized ratio (MELD-XI) score to predict adverse outcomes in infective endocarditis (IE) patients remains uncertain. This study was performed to explore the prognostic value of the MELD-XI score and modified MELD-XI score for patients with IE. A total of 858 patients with IE were consecutively enrolled and classified into two groups: MELD-XI ≤?10 (n?=?588) and MELD-XI >?10 (n?=?270). Multivariate analysis was performed to determine risk factors independent of MELD-XI score. Higher MELD-XI score was associated with higher in-hospital mortality (15.6 vs. 4.8%, p?<?0.001) and major adverse clinical events (33.3 vs. 18.4%, p?<?0.001). MELD-XI score was an independent predictor of in-hospital death (odds ratio [OR]?=?1.06, 95% CI, 1.02–1.10, p?=?0.005). Based on a multivariate analysis, NYHA class III or IV (3 points), C-reactive protein >?9.5 mg/L (4 points), and non-surgical treatment (6 points) were added to MELD-XI score. Modified MELD-XI score produced higher predictive power than previous (AUC 0.823 vs. 0.701, p?<?0.001). The cumulative incidence of long-term mortality (median 29 months) was significantly higher in patients with modified MELD-XI score >?13 than those without (log-rank?=?25.30, p?<?0.001). Modified MELD-XI score was independently associated with long-term mortality (hazard ratio?=?1.08, 95% CI, 1.04–1.12, p?<?0.001). MELD-XI score could be used as a risk assessment tool in IE. Furthermore, modified MELD-XI score remained simple and more effective in predicting poor prognosis.     

Clinical outcomes and treatment approach for community-associated methicillin-resistant <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> (CA-MRSA) infections in Israel

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are increasingly documented worldwide. We recently identified two major CA-MRSA clones in Israel: USA300 and t991. Here, we assessed clinical outcomes by CA-MRSA clones and the physicians’ treatment approach to CA-MRSA infections. All community-onset, clinical MRSA isolates detected during 2011–2013 by Maccabi Healthcare Services were collected and characterized phenotypically and genotypically; data were collected retrospectively from electronic medical records. Of 309 patients with MRSA infections, 64 were identified as CA-MRSA (21 %). Of the CA-MRSA infections, 72 % had skin and soft tissue infections (SSTIs), 38 % were Panton–Valentine leukocidin (PVL)+, the major clone being USA300 (n?=?13, 54 %). Of PVL? isolates (n?=?40, 62 %), t991 was the major clone. Age was the only predictor for PVL+ CA-MRSA infection (p?<?0.001). Patients with PVL+ CA-MRSA had higher incidence of SSTI recurrences (1.061 vs. 0.647 events per patient/per year, p?<?0.0001) and were more likely to have the SSTI drained (64 % vs. 21 %, p?=?0.003) when compared to PVL? CA-MRSA. USA300 was more common among adults, while t991 was more common among children (p?=?0.002). The physician’s referral to culture results and susceptibility were the only predictors of appropriate antibiotic therapy (p?<?0.001). However, only a minority of physicians referred to culture results, regardless of subspecialties. PVL+ CA-MRSA isolates caused significantly more recurrences of SSTIs and increased the need for drainage compared with PVL? isolates. Physicians’ awareness of CA-MRSA as a cause of SSTIs in the community was suboptimal. Culturing of pus-producing SSTIs is crucial for providing adequate antimicrobials and elucidating MRSA epidemiology.     

<Emphasis Type="Italic">Ureaplasma parvum</Emphasis> causes hyperammonemia in a pharmacologically immunocompromised murine model

A relationship between hyperammonemia and Ureaplasma infection has been shown in lung transplant recipients. We have demonstrated that Ureaplasma urealyticum causes hyperammonemia in a novel immunocompromised murine model. Herein, we determined whether Ureaplasma parvum can do the same. Male C3H mice were given mycophenolate mofetil, tacrolimus, and prednisone for 7 days, and then challenged with U. parvum intratracheally (IT) and/or intraperitoneally (IP), while continuing immunosuppression over 6 days. Plasma ammonia concentrations were determined and compared using Wilcoxon rank-sum tests. Plasma ammonia concentrations of immunosuppressed mice challenged IT/IP with spent broth (median, 188 μmol/L; range, 102–340 μmol/L) were similar to those of normal (median, 226 μmol/L; range, 154–284 μmol/L, p?>?0.05), uninfected immunosuppressed (median, 231 μmol/L; range, 122–340 μmol/L, p?>?0.05), and U. parvum IT/IP challenged immunocompetent (median, 226 μmol/L; range, 130–330 μmol/L, p?>?0.05) mice. Immunosuppressed mice challenged with U. parvum IT/IP (median 343 μmol/L; range 136–1,000 μmol/L) or IP (median 307 μmol/L; range 132–692 μmol/L) had higher plasma ammonia concentrations than those challenged IT/IP with spent broth (p?<?0.001). U. parvum can cause hyperammonemia in pharmacologically immunocompromised mice.     

Time to positivity of blood culture and its prognostic value in bloodstream infection

The purpose of this study was to investigate the relationship between the time to positivity (TTP) of blood cultures and outcome in patients with bloodstream infections (BSIs). Between January 1st, 2011 and December 31st, 2013, the blood cultures of inpatients with BSI or catheter-related BSI were collected at Peking University Third Hospital. The TTP of different isolates was analyzed, and the relationship between the TTP of isolates and outcome of patients with Enterobacter BSI was retrospectively analyzed. We analyzed the TTP of 886 isolates. Escherichia coli has the shortest (11.97?±?10.06 h) and Candida has the longest first TTP (61.62?±?42.77 h). 68.01 % of isolates reached positivity within 24 h and 88.33 % within 48 h. Over 90 % of E. coli isolates reached positivity within 24 h. Over 50 % of Candida isolates reached positivity within 48 h. The TTP differed significantly between cultures that were single or double positive for coagulase-negative staphylococci isolates, Enterobacteriaceae, and Pseudomonas aeruginosa, and between aerobic and anaerobic cultures of E. coli (p?<?0.05). However, the TTP did not differ significantly between coagulase-negative staphylococci (double positivity) and Staphylococcus aureus. The best TTP threshold for prediction of mortality from Enterobacter species BSI was 16.3 h [area under the curve (AUC) 0.730, 95 % confidence interval (CI) 0.557, 0.864, sensitivity 100 %, specificity 44.4 %]. The TTP of clinical isolates may represent a valuable marker of the clinical significance of BSIs. Laboratories and clinics should consider using the TTP to predict the prognosis of patients with BSI by bacteria, including Enterobacter and other species.     

Differences in clotting parameters between species for preclinical large animal studies of cardiovascular devices

Several species of domestic animals are used in preclinical studies evaluating the safety and feasibility of medical devices; however, the relevance of animal models to human health is often not clear. The purpose of this study was to compare the clotting parameters of animal models to determine which animals most adequately mimic human clotting parameters. The clotting parameters of the different species were assessed in whole blood by in vitro thromboelastography using the clotting activators, such as tissue factor (extrinsic clotting screening test, EXTEM^®) and partial thromboplastin phospholipid (intrinsic clotting screening test, IINTEM^®). The measurements were performed using normal blood samples from humans (n?=?13), calves (n?=?18), goats (n?=?56) and pigs (n?=?8). Extrinsic clotting time (CT) and the intrinsic CT were significantly prolonged in calves compared to humans (249.9?±?91.3 and 376.4?±?124.4 s vs. 63.5?±?11.8 and 192.5?±?29.0 s, respectively, p?<?0.01). The maximum clot firmness (MCF) in domestic animals (EXTEM^®: 77–87 mm, IINTEM^®: 66–78 mm) was significantly higher than that of humans (EXTEM^®: 59.1?±?6.0 mm, IINTEM^®: 58.8?±?1.5 mm, p?<?0.01), and calves and goats exhibited longer time to MCF (MCF-t) than did humans and pigs (p?<?0.01). Our results show that there are relevant differences in the four species’ extrinsic and intrinsic clotting parameters. These cross-comparisons indicate that it is necessary to clarify characteristics of clotting properties in preclinical animal studies.     

Efficacy evaluation of iclaprim in a neutropenic rat lung infection model with methicillin-resistant <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> entrapped in alginate microspheres

The objective of this study was to demonstrate the efficacy of iclaprim in a neutropenic rat lung infection model with methicillin-resistant Staphylococcus aureus (MRSA) entrapped in alginate beads. An inoculum of 5.25?×?10⁵ colony-forming units (CFU)/mL of S. aureus strain AH1252 was administered intratracheally to rats with prepared alginate bacteria suspensions. Beginning 2 h post-infection, rats received: (1) iclaprim 80 mg/kg (n?=?16); (2) iclaprim 60 mg/kg (n?=?16), or (3) vancomycin 50 mg/kg (n?=?24), for 3 days via subcutaneous (SC) injection every 12 h. Twelve hours after the last treatment, rats were euthanized and lungs collected for CFU determination. Iclaprim administered at 80 mg/kg or 60 mg/kg or vancomycin 50 mg/kg SC twice a day for 3 days resulted in a 6.05 log₁₀ CFU reduction (iclaprim 80 mg/kg compared with control, p?<?0.0001), 5.11 log₁₀ CFU reduction (iclaprim 60 mg/kg compared with control, p?<?0.0001), and 3.42 log₁₀ CFU reduction, respectively, from the controls (p?<?0.0001). Iclaprim 80 mg/kg and 60 mg/kg resulted in 2.59 and 1.69 log₁₀ CFU reductions, respectively, from vancomycin-treated animals (80 mg/kg iclaprim vs. vancomycin, p?=?0.0005; 60 mg/kg iclaprim vs. vancomycin, p?=?0.07). Animals receiving iclaprim, vancomycin, and controls demonstrated 100%, 91.7%, and 48.3% survival, respectively. In this neutropenic rat S. aureus lung infection model, rats receiving iclaprim demonstrated a greater CFU reduction than the controls or those receiving vancomycin.     

Effect of Kalpaamruthaa on immunosuppression of both humoral and cell-mediated immunity in DMBA-induced mammary tumours of rats

The present study was carried out to elucidate the protective effect of Kalpaamruthaa on improving 7,12-dimethylbenz(a)anthracene (DMBA)-induced immunosuppression of both humoral and cell-mediated immunity in mammary carcinoma-induced rats. Breast cancer was induced in rats by administering DMBA orally (25 mg/rat) as a single dose. After 90 days of induction, SA (200 mg/kg body weight) and KA (300 mg/kg body weight) were administered for 14 days, by gastric intubation. Several immunotoxicological assays such as T cell rosette delayed type hypersensitivity (DTH) response, migration inhibition factor (MIF) assay, lymphocyte proliferation assay, plaque forming cell (PFC) assay and haemagglutination assay, plaque forming cell (PFC) assay, serum soluble immune complex and cytokine production, T and B cell mitogenesis induced by Con A and nonspecific cell-mediated immunity were evaluated using phagocytosis activity and NBT reduction. In cancer-induced animals (group II), the leukocyte migration inhibition declined markedly (p?<?0.001), the levels of cytokines IFN-γ and IL-2 were significantly decreased (p?<?0.001) and also the antibody titre level (p?<?0.001) was significantly reduced when compared with control rats. A marked decline in PFC (p?<?0.001) and serum soluble immune complex (PEG) formation (p?<?0.001) was also observed. Hence, the present study clearly demonstrates the immunoprotective effect of KA.     

Infective endocarditis in patients with hepatic diseases

Few data have been published regarding the epidemiology and outcome of infective endocarditis (IE) in patients with chronic hepatic disease (CHD). A retrospective analysis of the Studio Endocarditi Italiano (SEI) database was performed to evaluate the epidemiology and outcome of CHD+ patients compared with CHD? patients. The diagnosis of IE was defined in accordance with the modified Duke criteria. Echocardiography, diagnosis, and treatment procedures were in accordance with current clinical practice. Among the 1722 observed episodes of IE, 300 (17.4 %) occurred in CHD+ patients. The cause of CHD mainly consisted of chronic viral infection. Staphylococcus aureus was the most common bacterial species in CHD+ patients; the frequency of other bacterial species (S. epidermidis, streptococci, and enterococci) were comparable among the two groups. The percentage of patients undergoing surgery for IE was 38.9 in CHD+ patients versus 43.7 in CHD? patients (p?=?0.06). Complications were more common among CHD+ patients (77 % versus 65.3 %, p?<?0.001); embolization (43.3 % versus 26.1 %, p?<?0.001) and congestive heart failure (42 % versus 34.1 %, p?=?0.01) were more frequent among CHD+ patients. Mortality was comparable (12.5 % in CHD? and 15 % in CHD+ patients). At multivariable analysis, factors associated with hospital-associated mortality were having an infection sustained by S. aureus, a prosthetic valve, diabetes and a neoplasia, and CHD. Being an intravenous drug user (IVDU) was a protective factor and was associated with a reduced death risk. CHD is a factor worsening the prognosis in patients with IE, in particular in patients for whom cardiac surgery was required.     

Quality of documentation on antibiotic therapy in medical records: evaluation of combined interventions in a teaching hospital by repeated point prevalence survey

This study aimed to improve the quality of documentation on antibiotic therapy in the computerized medical records of inpatients. A prospective, uncontrolled, interrupted time series (ITS) study was conducted by repeated point prevalence survey (PPS) to audit the quality of documentation on antibiotic therapy in the medical records before and after a combined intervention strategy (implementation of guidelines, distribution of educational materials, educational outreach visits, group educational interactive sessions) from the antimicrobial stewardship team (AST) in the academic teaching hospital (CHU) of Liège, Belgium. The primary outcome measure was the documentation rate on three quality indicators in the computerized medical records: (1) indication for treatment, (2) antibiotics prescribed, and (3) duration or review date. Segmented regression analysis was used to analyze the ITS. The medical records of 2306 patients receiving antibiotics for an infection (1177 in the pre-intervention period and 1129 in the post-intervention period) were analyzed. A significant increase in mean percentages in the post-intervention period was observed as compared with the pre-intervention period for the three quality indicators (indication documented 83.4?±?10.4 % vs. 90.3?±?6.6 %, p?=?0.0013; antibiotics documented 87.9?±?9.0 % vs. 95.6?±?5.1 %, p?<?0.0001; and duration or review date documented 31.9?±?15.4 % vs. 67.7?±?15.2 %, p?<?0.0001). The study demonstrated the successful implementation of a combined intervention strategy from the AST. This strategy was associated with significant changes in the documentation rate in the computerized medical records for the three quality indicators.     

Is 5 days of oral fluoroquinolone enough for acute uncomplicated pyelonephritis? The DTP randomized trial

The treatment duration of acute uncomplicated pyelonephritis (AUP) is still under debate. As shortening treatment duration could be a means to reduce antimicrobial resistance, we aimed to establish whether 5 days of antibiotic treatment is non-inferior to 10 days in patients with AUP. We performed an open-label prospective randomized trial comparing 5 days to 10 days of fluoroquinolone treatment for AUP. The inclusion criteria were: female patients aged ≥18 years with clinical signs of urinary tract infection, fever >38 °C, and positive urinalysis. Patients were randomized to either 5 or 10 days of fluoroquinolone treatment. Outcome was cure at day 10 and day 30 after the end of treatment. One hundred patients were randomized and 12 were excluded after randomization. The mean?±?standard deviation (SD) age was 31.8?±?11 years old and the mean?±?SD temperature was 38.6?±?0.7 °C. The main bacterium involved was Escherichia coli (n?=?86; 97.7%) and 3 (3.4%) patients had a positive blood culture. In the post-hoc analysis, clinical cure 10 days after the end of the treatment was 28/30 (93.3%) in the 5-day arm and 36/38 (94.7%) in the 10-day arm (p?=?1.00). At day 30, the clinical cure rate was 23/23 (100%) in the 5-day arm and 20/20 (100%) in the 10-day arm (p?=?1.00). The microbiological cure rate was 20/23 (87.0%) in the 5-day arm and 16/20 (80.0%) in the 10-day arm (p?=?1.00). The efficacy of 5 days of fluoroquinolone treatment does not seem different from 10 days of treatment for AUP.     

Implementing a practice change: early initiation of continuous renal replacement therapy during neonatal extracorporeal life support standardizes care and improves short-term outcomes

Purpose

We hypothesized that a standardized approach to early continuous renal replacement therapy (CRRT) during neonatal extracorporeal life support (ECLS) results in greater homogeneity of CRRT initiation times with improvements in fluid balance and outcomes.

Methods

Retrospective analysis of data (2007–2015) obtained from neonates treated prior to (E1; n?=?32) and after (E2; n?=?31) a 2011 practice change: CRRT initiation within 48 h of ECLS.

Results

Birthweight, gestational age, ECLS mode, and age at ECLS initiation were similar to each epoch. Survival [E1: median 75%, E2: 71%] and length of ECLS [E1: median 221 h, E2: 180 h] were comparable. During E2, 100% of infants received CRRT (vs. E1: 37%; p?<?0.001) and 97% of infants initiated CRRT within 48 h of ECLS (vs. E1: 13%; p?<?0.001). Control charts demonstrate reduced practice variation. Elapsed time from ECLS to CRRT differed between Epochs [E1: median 105 h, E2: 9 h; p?<?0.001] as did weight at CRRT initiation [E1: 4.13 kg (29% above baseline), E2: 3.19 kg (0%); p?<?0.001]. Significant differences in weight change were noted on days 6 and 7 (E1: 14%, E2: 2%; raw data comparison yielded p?<?0.05) and curves were different (p?<?0.05).

Conclusions

We successfully implemented a practice change, initiating CRRT within 48 h of ECLS cannulation, leading to decreased practice variation and improved short-term outcomes including decreased weight gain at CRRT initiation and faster return to baseline weight during the first 7 days of ECLS. We did not demonstrate changes in duration of ECLS, invasive ventilation, or survival.