Differences in Acinetobacter baumannii Strains and Host Innate Immune Response Determine Morbidity and Mortality in Experimental Pneumonia

Despite many reports documenting its epidemicity, little is known on the interaction of Acinetobacter baumannii with its host. To deepen our insight into this relationship, we studied persistence of and host response to different A. baumannii strains including representatives of the European (EU) clones I–III in a mouse pneumonia model. Neutropenic mice were inoculated intratracheally with five A. baumannii strains and an A. junii strain and at several days morbidity, mortality, bacterial counts, airway inflammation, and chemo- and cytokine production in lungs and blood were determined. A. baumannii RUH875 and RUH134 (EU clone I and II, respectively) and sporadic strain LUH8326 resulted in high morbidity/mortality, whereas A. baumannii LUH5875 (EU clone III, which is less widespread than clone I and II) caused less symptoms. A. baumannii type strain RUH3023T and A. junii LUH5851 did not cause disease. All strains, except A. baumannii RUH3023T and A. junii LUH5851, survived and multiplied in the lungs for several days. Morbidity and mortality were associated with the severity of lung pathology and a specific immune response characterized by low levels of anti-inflammatory (IL-10) and specific pro-inflammatory (IL-12p40 and IL-23) cytokines at the first day of infection. Altogether, a striking difference in behaviour among the A. baumannii strains was observed with the clone I and II strains being most virulent, whereas the A. baumannii type strain, which is frequently used in virulence studies appeared harmless

Completing the Enalaprilat Excretion Pathway-Renal Handling by the Proximal Tubule

: Background: Enalapril is often used in the treatment of cardiovascular diseases. Clinical data suggest that the urinary excretion of enalaprilat, the active metabolite of enalapril, is mediated by renal transporters. We aimed to identify enalaprilat specificity for renal proximal tubular transporters. Methods: Baculovirus-transduced HEK293 cells overexpressing proximal tubular transporters were used to study enalaprilat cellular uptake. Uptake into cells overexpressing the basolateral transporters OCT2, OAT1, OAT2, or OAT3 and apical transporters OAT4, PEPT1, PEPT2, OCTN1, OCTN2, MATE1, MATE2k, and URAT1 was compared with mock-transduced control cells. Transport by renal efflux transporters MRP2, MPR4, P-gp, and BCRP was tested using a vesicular assay. Enalaprilat concentrations were measured using LC-MS/MS. Results: Uptake of enalaprilat into cells expressing OAT3 as well as OAT4 was significantly higher compared to control cells. The enalaprilat affinity for OAT3 was 640 (95% CI: 520–770) µM. For OAT4, no reliable affinity constant could be determined using concentrations up to 3 mM. No transport was observed for other transporters. Conclusion: The affinity of enalaprilat for OAT3 and OAT4 was notably low compared to other substrates. Taking this affinity and clinically relevant plasma concentrations of enalaprilat and other OAT3 substrates into account, we believe that drug–drug interactions on a transporter level do not have a therapeutic consequence and will not require dose adjustments of enalaprilat itself or other OAT3 substrates

Are pathogenic leptospira species agents of community-acquired pneumonia? case reports of leptospirosis presenting as pneumonia

We report four Indonesian cases meeting the clinical and radiological criteria for community-acquired pneumonia and other findings suggestive of leptospirosis. Quantitative PCR (qPCR) analyses of serum and urine samples and serology confirmed the diagnosis of leptospirosis in each. Results of qPCR analysis of throat swabs were concordant with those obtained with acutephase serum samples, which suggests its potential for use as a noninvasive diagnostic tool for leptospirosis

An evidence-based recommendation on bed head elevation for mechanically ventilated patients

A semi-upright position in ventilated patients is recommended to prevent ventilator-associated pneumonia (VAP) and is one of the components in the Ventilator Bundle of the Institute for Health Care Improvement. This recommendation, however, is not an evidence-based one.status: publishe

Diagnostic value of C reactive protein in infections of the lower respiratory tract: systematic review

Objectives To evaluate the diagnostic accuracy of C reactive protein in detecting radiologically proved pneumonia and to evaluate how well it can discriminate between bacterial and viral infections of the lower respiratory tract. Data sources Medline and Embase (January 1966 to April 2004), with reference checking. Study selection We included articles comparing C reactive protein with a chest radiograph or with microbiological work-up as a reference test. Two authors independently assessed methodological items. Results None of the studies met all validity criteria. Six studies used an infiltrate on chest radiograph as reference test. Sensitivities ranged from 10% to 98%, specificities from 44% to 99%. For adults, the relation of C reactive protein with an infiltrate (in a subgroup analysis of five studies) showed an area under the curve of 0.80 (95% confidence interval 0.75 to 0.85). In 12 studies, the relation of C reactive protein with a bacterial aetiology of infection of the lower respiratory tract was studied. Sensitivities ranged from 8% to 99%, specificities from 27% to 95%. These data were epidemiologically and statistically heterogeneous, so overall outcomes could not be calculated. Conclusion Testing for C reactive protein is neither sufficiently sensitive to rule out nor sufficiently specific to rule in an infiltrate on chest radiograph and bacterial aetiology of lower respiratory tract infection. The methodological quality of the diagnostic studies is generally poor. The evidence not consistently and sufficiently supports a wide introduction of C reactive protein as a rapid test to guide antibiotics prescription

Urinary catheter policies for long-term bladder drainage

BackgroundPeople requiring long-term bladder draining commonly experience catheter-associated urinary tract infection and other problems.ObjectivesTo determine if certain catheter policies are better than others in terms of effectiveness, complications, quality of life and cost-effectiveness in long-term catheterised adults and children.Search methodsWe searched the Cochrane Incontinence Group Specialised Trials Register (searched 28 September 2011). Additionally, we examined all reference lists of identified trials.Selection criteriaAll randomised and quasi-randomised trials comparing catheter policies (route of insertion and use of antibiotics) for long-term (more than 14 days) catheterisation in adults and children.Data collection and analysisData were extracted by two reviewers independently and compared. Disagreements were resolved by discussion. Data were processed as described in the Cochrane Handbook. If the data in trials had not been fully reported, clarification was sought from the authors. When necessary, the incidence-density rates (IDR) and/or the incidence-density differences (IDD) within a certain time period were calculated.Main resultsEight trials met the inclusion criteria involving 504 patients in four cross-over and four parallel-group randomised controlled trials. Only two of the pre-stated six comparisons were addressed in these trials.Four trials compared antibiotic prophylaxis with antibiotics when clinically indicated. for patients using intermittent catheterisation, there were inconsistent findings about the effect of antibiotic prophylaxis on symptomatic urinary tract infection (UTI). Only one study found a significant difference in the frequency of UTI favouring prophylaxis. for patients using indwelling urethral catheterisation, one small trial reported fewer episodes of symptomatic UTI in the prophylaxis group. Four trials compared antibiotic prophylaxis with giving antibiotics when microbiologically indicated. for patients using intermittent catheterisation, there was limited evidence that receiving antibiotics reduced the rate of bacteriuria (asymptomatic and symptomatic). There was weak evidence that prophylactic antibiotics were better in terms of fewer symptomatic bacteriuria.Authors' conclusionsNo eligible trials were identified that compared alternative routes of catheter insertion. the data from eight trials comparing different antibiotic policies were sparse, particularly when intermittent catheterisation was considered separately from indwelling catheterisation. Possible benefits of antibiotic prophylaxis must be balanced against possible adverse effects, such as development of antibiotic resistant bacteria. These cannot be reliably estimated from currently available trials.National Health Service Research and Development Programme, UKUniversidade Federal de São Paulo, Dept Urol, BR-04105002 São Paulo, BrazilLeiden Univ, Med Ctr, Dept Infect Dis, Leiden, NetherlandsUniversidade Federal de São Paulo, Brazilian Cochrane Ctr, BR-04105002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Urol, BR-04105002 São Paulo, BrazilUniversidade Federal de São Paulo, Brazilian Cochrane Ctr, BR-04105002 São Paulo, BrazilWeb of Scienc

The Synthetic N-Terminal Peptide of Human Lactoferrin, hLF(1-11), Is Highly Effective against Experimental Infection Caused by Multidrug-Resistant Acinetobacter baumannii

The lactoferrin-derived peptide hLF(1-11), but not its control peptide, was highly effective against five multidrug-resistant Acinetobacter baumannii strains in vitro (3 to 4 log reduction) and against four of these strains in an experimental infection in mice (2 to 3 log reduction). Therefore, this peptide is a promising candidate as a novel agent against infections with multidrug-resistant A. baumannii