Dataset Information

An external ventricular drainage catheter impregnated with rifampicin, trimethoprim and triclosan, with extended activity against MDR Gram-negative bacteria: an in vitro and in vivo study.

ABSTRACT:

Background

External ventricular drainage (EVD) carries a high risk of ventriculitis, increasingly caused by MDR Gram-negative bacteria such as Escherichia coli and Acinetobacter baumannii. Existing antimicrobial EVD catheters are not effective against these, and we have developed a catheter with activity against MDR bacteria and demonstrated the safety of the new formulation for use in the brain.

Objectives

Our aim was to determine the ability of a newly formulated impregnated EVD catheters to withstand challenge with MDR Gram-negative bacteria and to obtain information about its safety for use in the CNS.

Methods

Catheters impregnated with three antimicrobials (rifampicin, trimethoprim and triclosan) were challenged in flow conditions at four weekly timepoints with high doses of MDR bacteria, including MRSA and Acinetobacter, and monitored for bacterial colonization. Catheter segments were also inserted intracerebrally into Wistar rats, which were monitored for clinical and behavioural change, and weight loss. Brains were removed after either 1?week or 4?weeks, and examined for evidence of inflammation and toxicity.

Results

Control catheters colonized quickly after the first challenge, while no colonization occurred in the impregnated catheters even after the 4?week challenge. Animals receiving the antimicrobial segments behaved normally and gained weight as expected. Neurohistochemistry revealed only surgical trauma and no evidence of neurotoxicity.

Conclusions

The antimicrobial catheter appears to withstand bacterial challenge for at least 4?weeks, suggesting that it might offer protection against infection with MDR Gram-negative bacteria in patients undergoing EVD. It also appears to be safe for use in the CNS.

SUBMITTER: Bayston R

PROVIDER: S-EPMC6753475 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Publications

An external ventricular drainage catheter impregnated with rifampicin, trimethoprim and triclosan, with extended activity against MDR Gram-negative bacteria: an in vitro and in vivo study.

Bayston Roger R Ashraf Waheed W Pelegrin Ivan I Fowkes Katherine K Bienemann Alison S AS Singleton William G B WGB Scott Ian S IS

The Journal of antimicrobial chemotherapy 20191001 10

<h4>Background</h4>External ventricular drainage (EVD) carries a high risk of ventriculitis, increasingly caused by MDR Gram-negative bacteria such as Escherichia coli and Acinetobacter baumannii. Existing antimicrobial EVD catheters are not effective against these, and we have developed a catheter with activity against MDR bacteria and demonstrated the safety of the new formulation for use in the brain.<h4>Objectives</h4>Our aim was to determine the ability of a newly formulated impregnated EVD ...[more]

PMID: 31302702

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Project description:To assess the efficacy of antimicrobial-impregnated catheters in preventing catheter-related infections during external ventricular drainage (EVD), we performed a meta-analysis and systematic review. We systematically searched Medline, Embase, and the Cochrane Library. All randomized controlled trials (RCTs) and nonrandomized prospective studies (NPSs) related to antimicrobial-impregnated EVD catheters were included. The primary outcome was the rate of cerebrospinal fluid infection (CFI). The secondary outcomes included the rate of time-dependent CFI and catheter bacterial colonization. We further performed subgroup analysis, meta-regression analysis, and microbial spectrum analysis. Four RCTs and four NPSs were included. The overall rate of CFIs was 3.6% in the antimicrobial-impregnated catheter group and 13.7% in the standard catheter group. The pooled data demonstrated that antimicrobial-impregnated catheters were superior to standard catheters in lowering the rate of CFIs (odds ratio (OR) = 0.25, 95% confidence interval (CI) = 0.12 to 0.52, P <0.05). In survival analysis, the 20-day infection rate was significantly reduced with the use of antimicrobial-impregnated catheters (hazard ratio = 0.52, 95% CI = 0.29 to 0.95, P <0.05). Furthermore, a significantly decreased rate of catheter bacterial colonization was noticed for antimicrobial-impregnated catheters (OR = 0.37, 95% CI = 0.21 to 0.64, P <0.05). In subgroup analyses, although significant results remained for RCTs and NPSs, a subgroup difference was revealed (P <0.05). Compared with standard catheters, a significantly lower rate of CFIs was noticed for clindamycin/rifampin-impregnated catheters (OR = 0.27, 95% CI = 0.10 to 0.73, P <0.05) and for minocycline/rifampin-impregnated catheters (OR = 0.11, 95% CI = 0.06 to 0.21, P <0.05). However, no statistical significance was found when compared with silver-impregnated catheters (OR = 0.33, 95% CI = 0.07 to 1.69, P = 0.18). In microbial spectrum analysis, antimicrobial-impregnated catheters were shown to have a lower rate of Gram-positive bacterial infection, particularly the coagulase-negative Staphylococcus. In conclusion, the use of antimicrobial-impregnated EVD catheters could be beneficial for the prevention of CFI and catheter bacterial colonization. Although antibiotic-coated catheters seem to be effective, no sufficient evidence supports the efficacy of silver-impregnated catheters.

Project description:Pseudomonas aeruginosa is the most common Gram-negative pathogen causing nosocomial multidrug resistant infections. It is a good biofilm producer and has the potential for contaminating medical devices. Despite the widespread use of antibacterial-impregnated catheters, little is known about the impacts of antibacterial coating on the pathogenesis of P. aeruginosa. In this study, we investigated the adaptive resistance potential of P. aeruginosa strain PAO1 in response to continuous antibiotic exposure from clindamycin/rifampicin-impregnated catheters (CR-IC). During exposure for 144 h to clindamycin and rifampicin released from CR-IC, strain PAO1 formed biofilms featuring elongated and swollen cells. There were 545 and 372 differentially expressed proteins (DEPs) identified in the planktonic and biofilm cells, respectively, by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Both Cluster of Orthologous Groups (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the planktonic cells responded to the released antibiotics more actively than the biofilm cells, with metabolism and ribosomal biosynthesis-associated proteins being significantly over-expressed. Exposure to CR-IC increased the invasion capability of P. aeruginosa for Hela cells and upregulated the expression of certain groups of virulence proteins in both planktonic and biofilm cells, including the outer membrane associated (flagella, type IV pili and type III secretion system) and extracellular (pyoverdine) virulence proteins. Continuous exposure of P. aeruginosa to CR-IC also induced the overexpression of antibiotic resistance proteins, including porins, efflux pumps, translation and transcription proteins. However, these upregulations did not change phenotypic minimum inhibitory concentration (MIC) during the experimental timeframe. The concerning association between CR-IC and overexpression of virulence factors in P. aeruginosa suggests the need for additional investigation to determine if it results in adverse clinical outcomes.

Project description:Background:A multitude of definitions determining multidrug resistance (MDR) of Gram-negative organisms exist worldwide. The definitions differ depending on their purpose and on the issueing country or organization. The MDR definitions of the European Centre for Disease Prevention and Control (ECDC) were primarily chosen to harmonize epidemiological surveillance. The German Commission of Hospital Hygiene and Infection Prevention (KRINKO) issued a national guideline which is mainly used to guide infection prevention and control (IPC) measures. The Swiss University Hospital Zurich (UHZ) - in absentia of national guidelines - developed its own definition for IPC purposes. In this study we aimed to determine the effects of different definitions of multidrug-resistance on rates of Gram-negative multidrug-resistant organisms (GN-MDRO). Methods:MDR definitions of the ECDC, the German KRINKO and the Swiss University Hospital Zurich were applied on a dataset comprising isolates of Escherichia coli, Klebsiella pneumoniae, Enterobacter sp., Pseudomonas aeruginosa, and Acinetobacter baumannii complex. Rates of GN-MDRO were compared and the percentage of patients with a GN-MDRO was calculated. Results:In total 11'407 isolates from a 35?month period were included. For Enterobacterales and P. aeruginosa, highest MDR-rates resulted from applying the 'ECDC-MDR' definition. 'ECDC-MDR' rates were up to four times higher compared to 'KRINKO-3/4MRGN' rates, and up to six times higher compared to UHZ rates. Lowest rates were observed when applying the 'KRINKO-4MRGN' definitions. Comparing the 'KRINKO-3/4MRGN' with the UHZ definitions did not show uniform trends, but yielded higher rates for E. coli and lower rates for P. aeruginosa. On the patient level, the percentages of GN-MDRO carriers were 2.1, 5.5, 6.6, and 18.2% when applying the 'KRINKO-4MRGN', 'UHZ-MDR', 'KRINKO-3/4MRGN', and the 'ECDC-MDR' definition, respectively. Conclusions:Different MDR-definitions lead to considerable variation in rates of GN-MDRO. Differences arise from the number of antibiotic categories required to be resistant, the categories and drugs considered relevant, and the antibiotic panel tested. MDR definitions should be chosen carefully depending on their purpose and local resistance rates, as definitions guiding isolation precautions have direct effects on costs and patient care.

Project description:The treatment of multidrug-resistant Gram-negative bacteria (MDR-GNB) infections in critically ill patients presents many challenges. Since an effective treatment should be administered as soon as possible, resistance to many antimicrobial classes almost invariably reduces the probability of adequate empirical coverage, with possible unfavorable consequences. In this light, readily available patient's medical history and updated information about the local microbiological epidemiology remain critical for defining the baseline risk of MDR-GNB infections and firmly guiding empirical treatment choices, with the aim of avoiding both undertreatment and overtreatment. Rapid diagnostics and efficient laboratory workflows are also of paramount importance both for anticipating diagnosis and for rapidly narrowing the antimicrobial spectrum, with de-escalation purposes and in line with antimicrobial stewardship principles. Carbapenem-resistant Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii are being reported with increasing frequencies worldwide, although with important variability across regions, hospitals and even single wards. In the past few years, new treatment options, such as ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, plazomicin, and eravacycline have become available, and others will become soon, which have provided some much-awaited resources for effectively counteracting severe infections due to these organisms. However, their optimal use should be guaranteed in the long term, for delaying as much as possible the emergence and diffusion of resistance to novel agents. Despite important progresses, pharmacokinetic/pharmacodynamic optimization of dosages and treatment duration in critically ill patients has still some areas of uncertainty requiring further study, that should take into account also resistance selection as a major endpoint. Treatment of severe MDR-GNB infections in critically ill patients in the near future will require an expert and complex clinical reasoning, of course taking into account the peculiar characteristics of the target population, but also the need for adequate empirical coverage and the more and more specific enzyme-level activity of novel antimicrobials with respect to the different resistance mechanisms of MDR-GNB.

Project description:BackgroundBurr hole evacuation is a well-established treatment for symptomatic cases with chronic subdural hematoma (cSDH). Routinely postoperative catheter is left in the subdural space to drain the residual blood. Drainage obstruction is commonly seen, and it can be related to suboptimal treatment.MethodsTwo groups of patients submitted to cSDH surgery were evaluated in a retrospective non-randomized trial, one group that had conventional subdural drainage (CD group, n = 20) and another group that used an anti-thrombotic catheter (AT group, n = 14). We compared the obstruction rate, amount of drainage and complications. Statistical analyses were done using SPSS (v.28.0).ResultsFor AT and CD groups respectively (median ± IQR), the age was 68.23 ± 26.0 and 70.94 ± 21.5 (p > 0.05); preoperative hematoma width was 18.3 ± 11.0 mm and 20.7 ± 11.7 mm and midline shift was 13.0 ± 9.2 and 5.2 ± 8.0 mm (p = 0.49). Postoperative hematoma width was 12.7 ± 9.2 mm and 10.8 ± 9.0 mm (p < 0.001 intra-groups compared to preoperative) and MLS was 5.2 ± 8.0 mm and 1.5 ± 4.3 mm (p < 0.05 intra-groups). There were no complications related to the procedure including infection, bleed worsening and edema. No proximal obstruction was observed on the AT, but 8/20 (40%) presented proximal obstruction on the CD group (p = 0.006). Daily drainage rates and length of drainage were higher in AT compared to CD: 4.0 ± 1.25 days vs. 3.0 ± 1.0 days (p < 0.001) and 69.86 ± 106.54 vs. 35.00 ± 59.67 mL/day (p = 0.074). Symptomatic recurrence demanding surgery occurred in two patients of CD group (10%) and none in AT group (p = 0.230), after adjusting for MMA embolization, there was still no difference between groups (p = 0.121).ConclusionThe anti-thrombotic catheter for cSDH drainage presented significant less proximal obstruction than the conventional one and higher daily drainage rates. Both methods demonstrated to safe and effective for draining cSDH.

Dataset Information

An external ventricular drainage catheter impregnated with rifampicin, trimethoprim and triclosan, with extended activity against MDR Gram-negative bacteria: an in vitro and in vivo study.

Background

Objectives

Methods

Results

Conclusions

Publications

An external ventricular drainage catheter impregnated with rifampicin, trimethoprim and triclosan, with extended activity against MDR Gram-negative bacteria: an in vitro and in vivo study.

Similar Datasets

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