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Insertion of a ventriculoperitoneal shunt for hydrocephalus is one of the commonest neurosurgical procedures worldwide. Infection of the implanted shunt affects up to 15% of these patients, resulting in prolonged hospital treatment, multiple surgeries, and reduced cognition and quality of life. Our aim was to determine the clinical and cost-effectiveness of antibiotic (rifampicin and clindamycin) or silver shunts compared with standard shunts at reducing infection. In this parallel, multicentre, single-blind, randomised controlled trial, we included patients with hydrocephalus of any aetiology undergoing insertion of their first ventriculoperitoneal shunt irrespective of age at 21 regional adult and paediatric neurosurgery centres in the UK and Ireland. Patients were randomly assigned (1:1:1 in random permuted blocks of three or six) to receive standard shunts (standard shunt group), antibiotic-impregnated (0·15% clindamycin and 0·054% rifampicin; antibiotic shunt group), or silver-impregnated shunts (silver shunt group) through a randomisation sequence generated by an independent statistician. All patients and investigators who recorded and analysed the data were masked for group assignment, which was only disclosed to the neurosurgical staff at the time of operation. Participants receiving a shunt without evidence of infection at the time of insertion were followed up for at least 6 months and a maximum of 2 years. The primary outcome was time to shunt failure due the infection and was analysed with Fine and Gray survival regression models for competing risk by intention to treat. This trial is registered with ISRCTN 49474281. Between June 26, 2013, and Oct 9, 2017, we assessed 3505 patients, of whom 1605 aged up to 91 years were randomly assigned to receive either a standard shunt (n=536), an antibiotic-impregnated shunt (n=538), or a silver shunt (n=531). 1594 had a shunt inserted without evidence of infection at the time of insertion (533 in the standard shunt group, 535 in the antibiotic shunt group, and 526 in the silver shunt group) and were followed up for a median of 22 months (IQR 10–24; 53 withdrew from follow-up). 32 (6%) of 533 evaluable patients in the standard shunt group had a shunt revision for infection, compared with 12 (2%) of 535 evaluable patients in the antibiotic shunt group (cause-specific hazard ratio [csHR] 0·38, 97·5% CI 0·18–0·80, p=0·0038) and 31 (6%) of 526 patients in the silver shunt group (0·99, 0·56–1·74, p=0·96). 135 (25%) patients in the standard shunt group, 136 (25%) in the antibiotic shunt group, and 140 (27%) in the silver shunt group had adverse events, which were not life-threatening and were mostly related to valve or catheter function. The BASICS trial provides evidence to support the adoption of antibiotic shunts in UK patients who are having their first ventriculoperitoneal shunt insertion. This practice will benefit patients of all ages by reducing the risk and harm of shunt infection. UK National Institute for Health Research Health Technology Assessment programme.

Purpose Compare the effectiveness of different cutaneous antiseptics in reducing risk of catheter-related infection in intensive care unit (ICU) patients. Methods We compared the risk of central venous catheter-related infection according to four-step (scrub, rinse, dry, and disinfect) alcoholic 5 % povidone–iodine (PVI-a, n  = 1521), one-step (disinfect) alcoholic 2 % chlorhexidine (2 % CHX-a, n  = 1116), four-step alcoholic <1 % chlorhexidine (<1 % CHX-a, n  = 357), and four-step aqueous 10 % povidone–iodine (PVI, n  = 368) antiseptics used for cutaneous disinfection and catheter care during the 3SITES multicenter randomized controlled trial. Within this cohort, we performed a quasi-experimental study (i.e., before–after) involving the four ICUs which switched from PVI-a to 2 % CHX-a. We used propensity score matching (PSM, n  = 776) and inverse probability weighting treatment (IPWT, n  = 1592). The end point was the incidence of catheter-related infection (CRI) defined as catheter-related bloodstream infection (CRBSI) or a positive catheter tip culture plus clinical sepsis on catheter removal. Results In the cohort analysis and compared with PVI-a, the incidence of CRI was lower with 2 % CHX-a [adjusted hazard ratio (aHR), 0.51; 95 % confidence interval (CI) (0.28–0.96), p  = 0.037] and similar with <1 % CHX-a [aHR, 0.73; (0.36–1.48), p  = 0.37] and PVI [aHR, 1.50; 95 % CI (0.85–2.64), p  = 0.16] after controlling for potential confounders. In the quasi-experimental study and compared with PVI-a, the incidence of catheter-related infection was again lower with 2 % CHX-a after PSM [HR, 0.35; 95 % CI (0.15, 0.84), p  = 0.02] and in the IPWT analysis [HR, 0.31; 95 % CI (0.14, 0.70), p  = 0.005]. The incidence of CRBSI or adverse event was not significantly different between antiseptics in all analyses. Conclusions In comparison with PVI-a, the use of 2 % CHX-a for cutaneous disinfection of the central venous catheter insertion site and maintenance catheter care was associated with a reduced risk of catheter infection, while the benefit of <1 % CHX-a was uncertain. Clinical trials identifier: NCT01479153.

Skin colonisation is an important source for central venous catheter (CVC) colonisation and infection. This study intended to identify risk factors for skin colonisation prior to CVC placement (baseline colonisation) and within 10 days after CVC insertion (subsequent colonisation), for CVC-tip colonisation and for bloodstream infection (BSI). Within a randomised clinical trial, data of 219 patients with haematological malignancies and inserted CVC (with a total of 5,501 CVC-days and 4,275 days at risk) in two university hospitals were analysed. Quantitative skin cultures were obtained from the insertion site before CVC placement and at regular intervals afterwards. CVC-tip cultures were taken on CVC removal and data collection was performed. Statistical analysis included linear and logistic regression models. Age was an independent risk factor for colonisation prior to CVC placement (baseline colonisation). Independent risk factors for subsequent colonisation were baseline colonisation and male gender. High level of subsequent skin colonisation at the insertion site was a predictor of CVC-tip colonisation, and a predictor of BSI. High level of skin colonisation predicts catheter tip colonisation and possibly subsequent infection. Sustained reduction of bacterial growth at the CVC insertion site is therefore indispensable. Male patients are at particular risk for skin colonisation and may be a target population for additional insertion-site care before and during catheterisation.

Objective: To measure systemic silver absorption when using silver-impregnated alginate central catheter dressings in very low birth weight (VLBW) neonates and to monitor blood stream infection. Study Design: Fifty infants were enrolled in a prospective, randomized controlled trial lasting 28 days. Each patient was assigned to standard dressing or silver alginate (Algidex) group. Serum silver concentrations were obtained on day 1, 7, and 28. Result: Significant differences in mean serum silver concentrations for the treatment versus standard dressing group were observed using student’s t -test analysis. The silver alginate group had a 45.8% reduction in infection/1000 line days, although too few patients were enrolled to draw meaningful efficacy conclusions about prevention of blood stream infection. Conclusion: Mean serum silver concentrations in the treatment group were significantly higher than controls although below levels anticipated to result in toxicity. A large study evaluating reduced blood stream infections in VLBW infants is warranted.

Abstrac t Background In the management of bacteremia, positive repeat blood cultures (persistent bacteremia) are associated with increased mortality. However, blood cultures are costly and it is likely unnecessary to repeat them for many patients. We assessed predictors of persistent bacteremia that should prompt repeat blood cultures. Methods We conducted a retrospective cohort study of bacteremias at an academic hospital from April 2010 to June 2014. We examined variables associated with patients undergoing repeat blood cultures, and with repeat cultures being positive. A nested case control analysis was performed on a subset of patients with repeat cultures. Results Among 1801 index bacteremias, repeat cultures were drawn for 701 patients (38.9 %), and 118 persistent bacteremias (6.6 %) were detected. Endovascular source (adjusted odds ratio [aOR], 7.66; 95 % confidence interval [CI], 2.30-25.48), epidural source (aOR, 26.99; 95 % CI, 1.91-391.08), and Staphylococcus aureus bacteremia (aOR, 4.49; 95 % CI, 1.88-10.73) were independently associated with persistent bacteremia. Escherichia coli (5.1 %, P  = 0.006), viridans group (1.7 %, P  = 0.035) and β-hemolytic streptococci (0 %, P  = 0.028) were associated with a lower likelihood of persistent bacteremia. Patients with persistent bacteremia were less likely to have achieved source control within 48 h of the index event (29.7 % vs 52.5 %, P  < .001), but after variable reduction, source control was not retained in the final multivariable model. Conclusions Patients with S. aureus bacteremia or endovascular infection are at risk of persistent bacteremia. Achieving source control within 48 h of the index bacteremia may help clear the infection. Repeat cultures after 48 h are low yield for most Gram-negative and streptococcal bacteremias.

The aim of this study was to evaluate procalcitonin (PCT) diagnostic accuracy in discriminating gram-negative (GN) from gram-positive (GP) bloodstream infections and determining the relationship between PCT levels, infection sites, and pathogen types. Clinical and laboratory data were collected from patients with blood culture (BC)-positive sepsis between January 2014 and December 2015. PCT levels at different infection sites were compared, as was the presence of GN and GP bloodstream infection. A receiver operating characteristic (ROC) curve was generated to assess diagnostic accuracy. Of the 486 monomicrobial BCs, 254 (52.26%) were positive for GN bacteria (GNB), and 202 (42.18%) for GP bacteria (GPB). Median PCT levels were higher in BCs positive for GN (2.42ng/ml, IQR: 0.38–15.52) than in those positive for GPB (0.49ng/ml, IQR: 0.13–5.89) (P<0.001). In the ROC analysis to differentiate between GNB and GPB, the area under the curve was 0.628 (95% CI: 0.576–0.679). When the cutoffs for PCT were 10.335 and 15.000ng/ml, the specificity of GNB infection was 80.2% and 84.2%, respectively. PCT levels caused by GNB differed between Escherichia coli and Acinetobacter baumanni/Burkholderia cepacia, Klebsiella pneumonia and Acinetobacter baumanni. PCT levels caused by GPB differed between Staphylococcus epidermidis/Staphylococcus aureus and Staphylococcus hominis/Staphylococcus haemolyticus, Enterococcus faecium and Enterococcus faecalis/S.hominis/S. haemolyticus. Among patients with known infection sites, there were statistical differences in PCT levels between abdominal infection and pneumonia/infective endocarditis, urinary tract infection and pneumonia/catheter-related infection/infective endocarditis. PCT can distinguish between GNB and GPB infection, as well as between different bacterial species and infection sites.

Peripherally inserted central catheter (PICC)-related bloodstream infections (BSIs) are serious complications in breast cancer patients. Reliable early risk assessment remains limited. Female breast cancer patients (n = 384) receiving PICCs were retrospectively analyzed. Serum CGRP levels were measured by ELISA, while PD-1 and PD-L1 expression was quantified via qPCR. A 3-point BioScore was calculated by assigning one point per abnormal biomarker (CGRP < 42.817 pg/mL, PD-1 > 2.301, PD-L1 < 1.613). Patients were stratified into low (0), intermediate (1–2), or high (3) risk groups. The cohort was split into training (n = 269) and validation (n = 115) sets. BSIs occurred in 78 patients (20.3%). The BioScore demonstrated excellent discrimination (AUC 0.96 in training and 0.93 in validation) and good calibration (Hosmer–Lemeshow P  = 0.797 and 0.875). BSI rates rose with BioScore category. While the BioScore was derived from biomarker values measured at the time of clinical suspicion for BSI, its strong discriminatory performance suggests potential for earlier application, such as at routine follow-ups, pending prospective validation. The BioScore demonstrated excellent internal discrimination and calibration in a retrospective, single-center cohort. Further external and prospective validation is necessary before clinical use.

ObjectiveCentral line associated bloodstream infection (CLABSI) is an important cause of morbidity and mortality in the neonatal intensive care unit (NICU). We designed a CLABSI Prevention Package (CPP) to decrease NICU CLABSI rates, using evidence-proven interventions.DesignThis was a quality improvement (QI) project. Data collection was divided into three phases (pre-implementation, implementation and post implementation). SQUIRE2.0 guidelines were used to design, implement and report this QI initiative.SettingA tertiary care level 3 NICU at the Aga Khan University Hospital (AKUH), Karachi, Pakistan.PatientsAll patients admitted to the AKUH NICU from 1 January 2016 to 31 March 2018 who had a central line in place during their NICU admission.InterventionsCPP used evidence-based interventions focusing on hand hygiene, aseptic central line insertion techniques and central line care, prevention of fungal infections and nurse empowerment.Main outcome measuresCLABSI rates pre and post intervention were recorded. Secondary outcomes were risk factors for CLABSI, device (central line) utilisation ratio, CLABSI related mortality and micro-organism profile.ResultsCLABSI rates decreased from 17.1/1000 device days to 5.0/1000 device days (relative risk (RR)=0.36, CI=0.17–0.74). Device (central line) utilisation ratio declined from 0.30 to 0.25. Out of 613 patients enrolled in our study, 139 (22.7%) died. Mortality was higher in CLABSI group (n=20, 44%) as compared with non CLABSI group (n=119, 21.1%) (p<0.001). Gestational age of <27 weeks was an independent risk factor for CLABSI (RR=4.45, CI=1.10–18.25, p=0.03). A total of 158 pathogens were isolated among which 68 were associated with CLABSI. Gram-negative bacteria 31 (47.7%) were the most common cause of CLABSI. Ninety-seven (61%) micro-organisms were multi-drug resistant.ConclusionsCPP was effective in decreasing NICU CLABSI rates and can be used as a model to decrease NICU CLABSI rates in low or middle-income countries.

Introduction Peripherally inserted central catheter (PICC)-related bloodstream infections (BSIs) are severe complications in breast cancer patients undergoing chemotherapy. This study evaluated the diagnostic potential of calcitonin gene-related peptide (CGRP), programmed cell death protein-1 (PD-1), and its ligand (PD-L1) as biomarkers for PICC-related BSIs. Methods A total of 384 breast cancer patients with PICC placement were retrospectively identified from medical records, of these, 78 developed BSIs and 306 did not. Serum levels of CGRP, PD-1, and PD-L1 were measured using enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (qPCR), respectively, to evaluate their potential as diagnostic biomarkers for BSIs. Blood cultures were performed to confirm infections and identify pathogens. Results The BSIs group showed significantly lower CGRP and PD-L1 levels, and higher PD-1 expression and PD-1/PD-L1 ratios compared to the non-BSIs group (all P < 0.001). Receiver operating characteristic (ROC) curve analysis showed area under the curve (AUC) values of 0.84 for CGRP, 0.77 for PD-1, 0.70 for PD-L1, and 0.86 for the PD-1/PD-L1 ratio. Combined detection achieved an AUC of 0.96, with 88% sensitivity and 92% specificity. Gram-negative bacteria (59.8%) were the predominant pathogens, with Escherichia coli (29.3%) being the most common. Conclusion CGRP alone showed strong diagnostic utility, but combining CGRP, PD-1, and PD-L1 markedly enhanced accuracy. ELISA and qPCR detection of these markers provides results within hours, enabling earlier diagnosis than conventional blood cultures.

Neonates are at high risk for central line associated bloodstream infections (CLABSI). Biofilm formation is universal on indwelling catheters but why some biofilms seed the bloodstream to cause CLABSI is not clearly understood. With the objective to test the hypothesis that catheter biofilm microbiome in neonates with CLABSI differs than those without infection, we prospectively enrolled neonates (n = 30) with infected and uninfected indwelling central catheters. Catheters were collected at the time of removal, along with blood samples and skin swabs at the catheter insertion sites. Microbiomes of catheter biofilms, skin swabs and blood were evaluated by profiling the V4 region of the bacterial 16S rRNA gene using Illumina MiSeq sequencing platform. The microbial DNA load was higher from catheter biofilms of CLABSI patients without differences in alpha diversity when compared to that of the non-CLABSI neonates. Proteus and unclassified Staphylococcaceae were more abundant in infected catheter biofilms while Bradyrhizobium, Cloacibacterium, and Sphingomonas were more abundant in the uninfected catheters. A blood microbiome was detected in uninfected samples. The blood microbiome in CLABSI neonates clustered separately from the uninfected blood samples in beta diversity plots. We found that the microbiome signature in catheter biofilm and blood of neonates with CLABSI is different than the microbiomes of non-CLABSI neonates.