scholarly journals 773. Hypochlorous Acid Generating Electrochemical Catheter Prototype for Prevention of Intraluminal Infections

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S483-S484
Author(s):  
Laure Flurin ◽  
Edison J Cano Cevallos ◽  
Abdelrhman Mohamed ◽  
Kerryl Greenwood-Quaintance ◽  
Yash Raval ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Hypochlorous Acid ◽  
Central Line ◽  
Platinum Electrodes ◽  
Research Support ◽  
Material Support ◽  
Cell Counts ◽  
Review Course ◽  
Board Review

Abstract Background Central-line associated bloodstream infection (CLABSI) contributes to mortality and cost. While aseptic dressings and antibiotic-impregnated catheters can prevent extraluminal infections, intraluminal infections remain a source of CLABSIs with limited prevention options. Methods In this proof-of-concept study, an electrochemical intravascular catheter (e-catheter) prototype capable of electrochemically generating hypochlorous acid intraluminally on the surface of platinum electrodes polarized at a constant potential of 1.5 VAg/AgCl was developed. After 24h of pre-polarization at 1.5 VAg/AgCl, their activity was tested by inoculating four clinical isolates derived from catheter-related infections, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecium and Escherichia coli. Figure 1. In vitro catheter and e-catheter models. Results E-catheters generated a mean HOCl concentration of 15.86±4.03 μM and had a mean pH of 6.14±0.79. e-catheters prevented infections with all four species, with an average reduction of 8.41±0.61 log10 CFU/mL at 48h compared to controls. Figure 3. Measurement of pH and HOCl at 48 hours in polarized e-catheters. Each dot represents a replicate; bars represent means. Figure 4. Prevention of infection after 48 hours of polarization (24 hours of infections) using e-catheters (polarized and non-polarized) compared to blank catheters. * indicates statistically significant reduction of cell counts in polarized e-catheter compared to blank catheter (p <0.05). Conclusion Polarized e-catheters which generate low amounts of HOCl continuously should be further developed to prevent intraluminal infection. Disclosures Haluk Beyenal, Ph.D, patent (Other Financial or Material Support, HB holds a patent: Beyenal H CD, Fransson BA, Sultana ST. . 2018. Electrochemical reduction or prevention of infections. U.S. patent 20180207301A1, international patent WO/2017/011635.) Robin Patel, MD, 1928 Diagnostics (Consultant)BioFire Diagnostics (Grant/Research Support)ContraFect Corporation (Grant/Research Support)Curetis (Consultant)Hylomorph AG (Grant/Research Support)IDSA (Other Financial or Material Support, Editor's Stipend)Infectious Diseases Board Review Course (Other Financial or Material Support, Honoraria)Mammoth Biosciences (Consultant)NBME (Other Financial or Material Support, Honoraria)Netflix (Consultant)Next Gen Diagnostics (Consultant)PathoQuest (Consultant)PhAST (Consultant)Qvella (Consultant)Samsung (Other Financial or Material Support, Patent Royalties)Selux Diagnostics (Consultant)Shionogi & Co., Ltd. (Grant/Research Support)Specific Technologies (Consultant)TenNor Therapeutics Limited (Grant/Research Support)Torus Biosystems (Consultant)Up-to-Date (Other Financial or Material Support, Honoraria) Robin Patel, MD, BioFire (Individual(s) Involved: Self): Grant/Research Support; Contrafect (Individual(s) Involved: Self): Grant/Research Support; IDSA (Individual(s) Involved: Self): Editor's stipend; NBME, Up-to-Date and the Infectious Diseases Board Review Course (Individual(s) Involved: Self): Honoraria; Netflix (Individual(s) Involved: Self): Consultant; TenNor Therapeutics Limited (Individual(s) Involved: Self): Grant/Research Support; to Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, PhAST, Torus Biosystems, Mammoth Biosciences and Qvella (Individual(s) Involved: Self): Consultant

scholarly journals An Integrated HOCl-Producing E-Scaffold Is Active Against Monomicrobial and Polymicrobial Biofilms

2021 ◽  
Author(s):  
Laure Flurin ◽  
Yash S. Raval ◽  
Abdelrhman Mohamed ◽  
Kerryl E. Greenwood-Quaintance ◽  
Edison J. Cano ◽  
...  
Keyword(s):  
Low Dose ◽  
Hypochlorous Acid ◽  
Viable Cell ◽  
Chloride Ions ◽  
Resistant Bacteria ◽  
Wound Infections ◽  
Microbial Biofilms ◽  
Cell Counts ◽  
Acquired Antibiotic Resistance

Oxidizing agents like hypochlorous acid (HOCl) have antimicrobial activity. We developed an integrated electrochemical scaffold or ‘e-scaffold’ that delivers a continuous low dose of HOCl aimed at targeting microbial biofilms without exceeding concentrations toxic to humans, as a prototype of a device being developed to treat wound infections in humans. In this work, we tested the device against 33 isolates of bacteria (including isolates with acquired antibiotic resistance) grown as in vitro biofilms, alongside 12 combinations of dual-species in vitro biofilms. Biofilms were grown on the bottoms of 12-well plates for 24 hours. An integrated e-scaffold was placed atop each biofilm and polarized at 1.5V for 1, 2 or 4 hours. HOCl was produced electrochemically by oxidizing chloride ions (Cl-) in solution to chlorine (Cl2); dissolved Cl2 spontaneously dissociates in water to produce HOCl. The cumulative concentration of HOCl produced at the working electrode in each well was estimated to be 7.89, 13.46, and 29.50 mM after 1, 2 and 4 hours of polarization, respectively. Four hours of polarization caused an average reduction of 6.13 log10 CFU/cm2 (±1.99 log10 CFU/cm2) of viable cell counts of mono-species biofilms and 5.53 log10 CFU/cm2 (±2.31 log10 CFU/cm2) for the 12 dual-species biofilms studied. The described integrated e-scaffold reduces viable bacterial cell counts in biofilms formed by an array of antibiotic-susceptible and -resistant bacteria alone and in combination.

scholarly journals 1309. Imipenem/Cilastatin/Relebactam (I/R) Alone and in Combination against Pseudomonas aeruginosa (PSA) in the In Vitro Pharmacodynamic Model

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S667-S667
Author(s):  
Iris H Chen ◽  
David P Nicolau ◽  
Joseph L Kuti
Keyword(s):  
Total Daily Dose ◽  
Combination Regimen ◽  
Bacterial Burden ◽  
Research Support ◽  
Material Support ◽  
The Difference ◽  
Combination Regimens ◽  
Log Ratio ◽  
Research Grant

Abstract Background I/R, a carbapenem-beta-lactamase inhibitor antibiotic, is active against most imipenem-resistant PSA, including MDR isolates. Combination therapy may enhance activity against MDR pathogens and suppress resistance. This study’s objective was to assess the efficacy of I/R compared with combinations including colistin (CST) or amikacin (AMK) against PSA in an IVPD model. Methods Human-simulated concentrations of I/R 500/250 mg every six hours, a total daily dose of CST 360 mg, and AMK 25 mg/kg daily were reproduced alone and in combination against 6 imipenem-non-susceptible PSA with I/R MICs of 1/4 to 8/4 mg/L in an IVPD over 24h. The primary endpoint was the difference in 24h colony forming units (CFU) between each combination regimen and its components alone. The log ratio differences of the area under the CFU curve were also calculated to compare the overall bacterial burden resulting from exposure to I/R alone with those treated by combination regimens. Emergence of resistance was tested at 24h using drug-containing plates at 3xMIC. Results I/R, CST, and AMK alone produced 24hCFU changes consistent with isolate MICs. One isolate (already I/R non-susceptible) developed I/R resistance, and 4 and 3 developed CST and AMK resistance, respectively. I/R plus CST suppressed all resistance and resulted in synergistic or additive interactions against three of six isolates with 24h CFU reductions ranging from -2.62 to -4.67 log10CFU/mL. This combination further reduced overall bacterial burden by 79-81% compared with I/R alone against two I/R-non-susceptible strains. I/R plus AMK also prevented resistance emergence but exhibited indifferent interactions against all isolates at 24h with the combined drugs achieving -0.51 to -3.33 log10CFU/mL reductions. Minor overall reductions in bacterial burden were observed relative to I/R alone. Conclusion I/R plus CST resulted in additivity or synergy against three of six PSA and prevented I/R and CST resistance, whereas the addition of AMK only suppressed resistance. The greatest overall reductions in bacterial burden, however, were observed with I/R plus CST against I/R-non-susceptible isolates, supporting targeted use of this combination against this phenotype when alternatives are unavailable. Disclosures David P. Nicolau, PharmD, Cepheid (Other Financial or Material Support, Consultant, speaker bureau member or has received research support.)Merck & Co., Inc. (Consultant, Grant/Research Support, Speaker’s Bureau)Wockhardt (Grant/Research Support) Joseph L. Kuti, PharmD, Allergan (Speaker’s Bureau)bioMérieux (Research Grant or Support, Other Financial or Material Support, Speaker Honorarium)Melinta (Research Grant or Support)Merck & Co., Inc. (Research Grant or Support)Paratek (Speaker’s Bureau)Summit (Other Financial or Material Support, Research funding (clinical trials))

scholarly journals 1255. In Vitro Activity of Vancapticin against Methicillin-Resistant Staphylococcus aureus from Periprosthetic Joint Infection

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S645-S645
Author(s):  
Hye-Kyung Cho ◽  
Melissa J Karau ◽  
Kerryl E Greenwood-Quaintance ◽  
Karl A Hansford ◽  
Matthew A Cooper ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Periprosthetic Joint Infection ◽  
Mayo Clinic ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Joint Infection ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Research Support ◽  
Material Support

Abstract Background The vancapticins are modified vancomycin derivatives developed by adding membrane targeting motifs to the C-terminus of vancomycin. We determined the in vitro activity of a lead vancapticin candidate against periprosthetic joint infection-associated methicillin-resistant Staphylococcus aureus (MRSA) in the planktonic and biofilm states, and the effect of adding 0.002% polysorbate 80 (P-80; Sigma-Aldrich) on vancapticin susceptibility testing. Methods Thirty-seven clinical isolates of MRSA collected at Mayo Clinic (Rochester, Minnesota) were studied. Vancapticin minimum inhibitory concentrations (MICs) were determined using Clinical and Laboratory Standards Institutes guidelines. Minimum biofilm bactericidal concentrations (MBBCs) were determined using a pegged lid microtiter plate assay. Vancapticin MIC and MBBC values were assessed with and without P-80. Vancapticin, vancomycin, and dalbavancin biofilm time-kill assays were performed using biofilms formed by 10 MRSA isolates on Teflon coupons. Results Vancapticin MICs with and without P-80 ranged from 0.015 to 0.12 μg/mL and 0.25 to 1 μg/mL, respectively. Vancapticin MBBCs with and without P-80 ranged from 0.25 to 4 μg/mL and 1 to 8 μg/mL, respectively. Reductions of biofilm bacterial densities on Teflon coupons after 8 and 24 hours of incubation with vancapticin, vancapticin with P-80, vancomycin, or dalbavancin with P-80 were less than 3-log10 cfu/cm2 for all isolates tested. Conclusion Vancapticin has promising in vitro activity against planktonic MRSA and MRSA in a pegged lid biofilm assay, but was not bactericidal against biofilms on Teflon coupons. P-80 decreased vancapticin MICs and MBBCs. Disclosures Mark A. Blaskovich, PhD, MAB Consulting (Consultant)The University of Queensland (Employee, Grant/Research Support, Other Financial or Material Support, Inventor on patent) Robin Patel, MD, Accelerate Diagnostics (Grant/Research Support)CD Diagnostics (Grant/Research Support)Contrafect (Grant/Research Support)Curetis (Consultant)GenMark Diagnostics (Consultant)Heraeus Medical (Consultant)Hutchison Biofilm Medical Solutions (Grant/Research Support)Merck (Grant/Research Support)Next Gen Diagnostics (Consultant)PathoQuest (Consultant)Qvella (Consultant)Samsung (Other Financial or Material Support, Dr. Patel has a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued.)Selux Dx (Consultant)Shionogi (Grant/Research Support)Specific Technologies (Consultant)

scholarly journals 1134. The Effect of Telehealth Antimicrobial Stewardship Program on Antimicrobial Use in a Pediatric Intensive Care Unit

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S658-S658
Author(s):  
Mohammad Alghounaim ◽  
Ahmed Abdelmoniem ◽  
Mohamed Elseadawy ◽  
Mohammad Surour ◽  
Mohamed Basuni ◽  
...  
Keyword(s):  
Intensive Care ◽  
Infectious Diseases ◽  
Antimicrobial Stewardship ◽  
Pediatric Intensive Care ◽  
Antimicrobial Use ◽  
Antimicrobial Stewardship Program ◽  
Research Support ◽  
Material Support ◽  
Stewardship Program ◽  
Days Of Therapy

Abstract Background Inappropriate antimicrobial use is common in pediatric intensive care units (PICU). We aimed to evaluate the effect of telehealth antimicrobial stewardship program (ASP) on the rate of PICU antimicrobial use in a center without a local infectious diseases consultation service. Methods Aretrospective cohort study was performed between October 1st, 2018 and October 31st, 2020 in Farwaniyah Hospital PICU, a 20-bed unit. All pediatric patients who were admitted to PICU and received systemic antimicrobials during the study period were included and followed until hospital discharge. Patients admitted to the PICU prior to the study period but still receiving intensive care during the study period were excluded. Weekly prospective audit and feedback on antimicrobial use was provided starting October 8th, 2019 (post-ASP period) by the ASP team. A pediatric infectious diseases specialist would join ASP rounds remotely. Descriptive analyses and a pre-post intervention comparison of days of therapy (DOT) were used to assess the effectiveness of the ASP intervention Results There were 272 and 152 PICU admissions before and after initiation of ASP, respectively. Bronchiolitis and pneumonia were the most common admission diagnoses, together compromising 60.7% and 61.2% pre- and post-ASP. Requirement for respiratory support was higher post-ASP (76.5% vs 91.5%, p< 0.001). Average monthly antimicrobial use decreased from 92.2 (95% CI 74.5 to 100) to 48.5 DOT/1,000 patient-days (95% CI 24.6 to 72.2, P < 0.05) (figure). A decline in DOT was observed across all antibiotic classes, except for ceftriaxone and clarithromycin. No effect on length of PICU stay, hospital length of stay, or mortality was observed. Most (89.7%) ASP recommendations were followed fully or partially changes in antimicrobial days of therapy (DOT)/1,000 patient-days over time. The dashed line represents the start of the antimicrobial stewardship program (ASP) Conclusion In settings where infectious diseases services are not available, telehealth stewardship can be effectively implemented and associated with a significant reduction of antimicrobial use. Disclosures Jesse Papenburg, MD, AbbVie (Grant/Research Support, Other Financial or Material Support, Personal fees)Medimmune (Grant/Research Support)Sanofi Pasteur (Grant/Research Support)Seegene (Grant/Research Support, Other Financial or Material Support, Personal fees)

scholarly journals 13. Evaluation of Etest for Antibiotic Susceptibility and Minimum Inhibitory Concentration (MIC) Agreement Against pseudomonas Aeruginosa (psa) from Patients with Cystic Fibrosis (CF)

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S7-S8
Author(s):  
Maxwell J Lasko ◽  
Holly Huse ◽  
Joseph L Kuti ◽  
David P Nicolau
Keyword(s):  
Error Rates ◽  
Major Error ◽  
Research Support ◽  
In Vitro Susceptibility ◽  
Material Support ◽  
Minor Error ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
Research Grant

Abstract Background CF acute pulmonary exacerbations are often caused by PSA, including multi-drug resistant strains. Optimal antibiotic therapy is required to return lung function and should be guided by in vitro susceptibility results. There are sparse data on the performance of Etest relative to reference broth microdilution (BMD) for many newer drugs against CF PSA. Herein, we describe Etest performance with 10 anti-PSA antibiotics against CF isolates. Methods Contemporary, clinical PSA (n=105) isolated during pulmonary exacerbation from patients with CF were acquired from 3 US hospitals. MICs were assessed by BMD (reference) and Etest for aztreonam (ATM), cefepime (FEP), ceftazidime (CAZ), ceftazidime/avibactam (CZA), ceftolozane/tazobactam (C/T), ciprofloxacin (CIP), levofloxacin (LVX), meropenem (MEM), piperacillin/tazobactam (TZP), and tobramycin (TOB). Each respective MIC was completed in at least triplicate using the same inoculum between methods. Modal MICs for each method were compared by rates of essential agreement (EA), categorical agreement (CA), minor error (miE), major error (ME), and very major error (VME) rates. All miE, ME and VME were adjusted if within EA. Results Of the 105 PSA, 46% had a mucoid phenotype. Results are summarized in the Table. Median modal Etest MICs read 0–1 dilution higher (IQR: 0–1) than BMD. CA and EA ranged from 64–93% and 63–86%, respectively. Single VMEs occurred for ATM (2.9%) and CAZ (4.2%). For CZA, 2 VMEs were observed and both were within EA. Major errors were ≤3% except for ATM (3.3%), MEM (3.3%), CZA (5.3% with adjusted ME 2.1%*), and FEP (13%). Minor error rates were < 10% except for TZP, CIP, LEV, TOB, and FEP (13–29%), for which majority of miE were within EA (3/14, 11/16, 10/18, 13/19, 20/31, respectively). Performance was similar for non-mucoid and mucoid populations. Etest Performance Conclusion Etest methods performed well for most antibiotics against this challenging collection of PSA from CF patients. Laboratories should be cautious of miE and ME that may occur with certain antibiotics. Furthermore, our observations suggest laboratories confirm CZA results for isolates with MICs near the breakpoint. Disclosures Joseph L. Kuti, PharmD, Allergan (Speaker’s Bureau)bioMérieux (Research Grant or Support, Other Financial or Material Support, Speaker Honorarium)Melinta (Research Grant or Support)Merck & Co., Inc. (Research Grant or Support)Paratek (Speaker’s Bureau)Summit (Other Financial or Material Support, Research funding (clinical trials)) David P. Nicolau, PharmD, Cepheid (Other Financial or Material Support, Consultant, speaker bureau member or has received research support.)Merck & Co., Inc. (Consultant, Grant/Research Support, Speaker’s Bureau)Wockhardt (Grant/Research Support)

scholarly journals Direct Detection and Identification of Prosthetic Joint Pathogens in Synovial Fluid (SF) by Metagenomic Shotgun Sequencing

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S32-S32
Author(s):  
Morgan Ivy ◽  
Matthew Thoendel ◽  
Patricio Jeraldo ◽  
Kerryl Greenwood-Quaintance ◽  
Arlen D Hanssen ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Infectious Diseases ◽  
Direct Detection ◽  
Marker Gene ◽  
Shotgun Sequencing ◽  
Detection And Identification ◽  
Review Course ◽  
Board Review ◽  
Culture Positive ◽  
Culture Negative

Abstract Background Detection and identification of microorganism(s) involved in periprosthetic joint infection (PJI) can inform surgical management and directed antibiotic therapy. Metagenomic shotgun sequencing is a powerful tool with the potential to change how many PJIs are diagnosed as it allows direct detection and identification of pathogens in clinical specimens. In the largest series to date, we utilized a metagenomics-based approach applied to SF to define potential microbial etiologies of failed total knee arthroplasties (TKAs). Methods Synovial fluid was collected from 112 failed TKAs [74 PJI and 38 aseptic implant failure (AF)] via preoperative arthrocentesis. Cell count and differential, standardized culture and DNA-based metagenomic shotgun sequencing were performed. Human DNA was depleted using the MolYsis basic kit prior to DNA extraction, whole genome amplification, and sequencing. Taxonomic assignment of reads and pathogen identification was achieved using a pipeline incorporating k-mer- and marker gene-based classification software. A scheme for analysis and filtration of false-positives was created and applied, incorporating cut-offs for the number of reads, quality scores, and coverage across a reference genome. Patients were classified as having PJI using the IDSA criteria and expert review. Analyses were recorded as percent agreement, with 95% confidence intervals (CI), of metagenomics to SF culture. Results Metagenomic analysis identified the known pathogen in 54 (90%) (CI, 79.5%–96.2%) of the 60 culture-positive PJIs analyzed and one (2%) (CI, 0.0%–8.9%) potential polymicrobial infection not detected by culture. For the 14 culture-negative PJIs tested, metagenomics showed 79% (CI, 49.2%–95.3%) agreement for negative findings; potential pathogens were identified in three (21%) (CI, 4.7%–50.8%) culture-negative PJI cases, with one being polymicrobial. Of the 37 culture-negative AF cases, metagenomics showed 97% (CI, 85.8%–99.9%) agreement with negative culture and identified one (3%) (CI, 0.0%–14.2%) potential pathogen. For the one culture-positive AF case, metagenomic results were negative, suggesting possible culture contamination. Conclusion Metagenomic shotgun sequencing performed on SF can be used to diagnose PJI and may be particularly useful for culture-negative PJI. Disclosures R. Patel, ASM: Board Member, None; CD Diagnostics, BioFire, Curetis, Merck, Hutchison Biofilm Medical Solutions, Accelerate Diagnostics, Allergan, and The Medicines Company: Grant Investigator, Grant recipient; Curetis: Consultant, Monies paid to my employer; A patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued: Patents, Patents, any money is paid to my employer; Actelion: DSMB, Money paid to my employer; ASM and IDSA: Editor’s stipends, Editor’s stipends; NBME, Up-to-Date and the Infectious Diseases Board Review Course: NBME, Up-to-Date and the Infectious Diseases Board Review Course, Honoraria; Roche, ASM, and IDSA: Travel reimbursement, Travel reimbursement

scholarly journals 1602. Comparative Activity of Ceftolozane-Tazobactam (C/T) and Ceftazidime-Avibactam (CZA) against Pseudomonas aeruginosa (PSA) from Patients with Cystic Fibrosis (CF)

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S797-S797
Author(s):  
Maxwell J Lasko ◽  
David P Nicolau ◽  
Joseph L Kuti
Keyword(s):  
Treatment Options ◽  
Standard Of Care ◽  
Research Support ◽  
Current Standard ◽  
Material Support ◽  
Standard Of Care Treatment ◽  
Hospital Systems ◽  
Support Research ◽  
Research Grant

Abstract Background Acute pulmonary exacerbations (APE) are a frequent cause of hospitalization for patients with CF. PSA is among the most common pathogen implicated in CF APE. Due to repetitive antibiotic courses, multidrug resistance (MDR) must be considered leaving few available intravenous antibiotic options. CZA and C/T are newer anti-PSA antibiotics that have been used to treat CF APE, but little data are available to compare their in vitro activity. Methods Non-duplicate, contemporary, clinical PSA (n=105) isolates were acquired from 85 patients during CF APE from 3 US hospital systems. MICs were assessed in at least triplicate by reference broth microdilution for C/T, CZA, aztreonam (ATM), cefepime (FEP), ceftazidime (CAZ), ciprofloxacin (CIP), levofloxacin (LVX), meropenem (MEM), piperacillin/tazobactam (TZP), and tobramycin (TOB). Current CLSI breakpoints were used to define susceptibility. Activity was further assessed in MDR, CAZ and MEM non-susceptible (NS) phenotypes. Results The mean patient age at isolate retrieval was 31 years (IQR: 21-43), and 20% were under 18 years. Mucoid morphology was observed in 48 (46%) isolates, and MDR defined in 41 (39%). Rates of susceptibility (MIC50/MIC90/%S) were: C/T (1/4/92%), CZA (2/8/90%), CAZ (4/64/68%), TZP (8/256/67%), TOB (2/32/63%), MEM (1/32/58%), ATM (8/64/57%), FEP (8/≥128/50%), CIP (2/8/27%), and LVX (4/16/24%). A mucoid phenotype did not alter %S (non-mucoid vs. mucoid) for C/T (93 vs. 92%) or CZA (91 vs. 88%). Among the 41 MDR PSA, activity was 2/16/83% and 4/16/76% for C/T and CZA, respectively. C/T, CZA, and MEM %S was 77, 69, and 23% for the 35 CAZ-NS isolates. C/T, CZA, and CAZ %S was 84, 77, and 39% for MEM-NS isolates. Conclusion These contemporary PSA from patients with CF displayed low susceptibility rates to most β-lactams, fluoroquinolones, and tobramycin, and MDR was common. C/T and CZA retained similarly high susceptibility against these isolates, including MDR strains and CAZ-NS/MEM-NS phenotypes. These data justify that both CT and CZA may be considered for CF APE due to PSA non-susceptible to current standard of care treatment options. Disclosures David P. Nicolau, PharmD, Cepheid (Other Financial or Material Support, Consultant, speaker bureau member or has received research support.)Merck & Co., Inc. (Consultant, Grant/Research Support, Speaker’s Bureau)Wockhardt (Grant/Research Support) Joseph L. Kuti, PharmD, Allergan (Speaker’s Bureau)bioMérieux (Research Grant or Support, Other Financial or Material Support, Speaker Honorarium)Melinta (Research Grant or Support)Merck & Co., Inc. (Research Grant or Support)Paratek (Speaker’s Bureau)Summit (Other Financial or Material Support, Research funding (clinical trials))

Mechanisms involved in effects of antimicrobial peptides, bactenectins ChBac3.4, ChBac5, and mini-ChBac7.5Nb, on bacterial cells

2017 ◽  
pp. 43-50
Author(s):  
О.В. Шамова ◽  
М.С. Жаркова ◽  
П.М. Копейкин ◽  
Д.С. Орлов ◽  
Е.А. Корнева
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Activity ◽  
Innate Immunity ◽  
Infectious Diseases ◽  
Metabolic Activity ◽  
Capra Hircus ◽  
Bacterial Cells ◽  
Antibiotic Resistant ◽  
Resistant Strains

Антимикробные пептиды (АМП) системы врожденного иммунитета - соединения, играющие важную роль в патогенезе инфекционных заболеваний, так как обладают свойством инактивировать широкий спектр патогенных бактерий, обеспечивая противомикробную защиту живых организмов. В настоящее время АМП рассматриваются как потенциальные соединения-корректоры инфекционной патологии, вызываемой антибиотикорезистентными бактериями (АБР). Цель данной работы состояла в изученим механизмов антибактериального действия трех пептидов, принадлежащих к семейству бактенецинов - ChBac3.4, ChBac5 и mini-ChBac7.5Nb. Эти химически синтезированные пептиды являются аналогами природных пролин-богатых АМП, обнаруженных в лейкоцитах домашней козы Capra hircus и проявляющих высокую антимикробную активность, в том числе и в отношении грамотрицательных АБР. Методы. Минимальные ингибирующие и минимальные бактерицидные концентрации пептидов (МИК и МБК) определяли методом серийных разведений в жидкой питательной среде с последующим высевом на плотную питательную среду. Эффекты пептидов на проницаемость цитоплазматической мембраны бактерий для хромогенного маркера исследовали с использованием генетически модифицированного штамма Escherichia coli ML35p. Действие бактенецинов на метаболическую активность бактерий изучали с применением маркера резазурина. Результаты. Показано, что все исследованные пептиды проявляют высокую антимикробную активность в отношении Escherichia coli ML35p и антибиотикоустойчивых штаммов Escherichia coli ESBL и Acinetobacter baumannii in vitro, но их действие на бактериальные клетки разное. Использован комплекс методик, позволяющих наблюдать в режиме реального времени динамику действия бактенецинов в различных концентрациях (включая их МИК и МБК) на барьерную функцию цитоплазматической мембраны и на интенсивность метаболизма бактериальных клеток, что дало возможность выявить различия в характере воздействия бактенецинов, отличающихся по структуре молекулы, на исследуемые микроорганизмы. Установлено, что действие каждого из трех исследованных бактенецинов в бактерицидных концентрациях отличается по эффективности нарушения целостности бактериальных мембран и в скорости подавления метаболизма клеток. Заключение. Полученная информация дополнит существующие фундаментальные представления о механизмах действия пролин-богатых пептидов врожденного иммунитета, а также послужит основой для биотехнологических исследований, направленных на разработку на базе этих соединений новых антибиотических препаратов для коррекции инфекционных заболеваний, вызываемых АБР и являющимися причинами тяжелых внутрибольничных инфекций. Antimicrobial peptides (AMPs) of the innate immunity are compounds that play an important role in pathogenesis of infectious diseases due to their ability to inactivate a broad array of pathogenic bacteria, thereby providing anti-microbial host defense. AMPs are currently considered promising compounds for treatment of infectious diseases caused by antibiotic-resistant bacteria. The aim of this study was to investigate molecular mechanisms of the antibacterial action of three peptides from the bactenecin family, ChBac3.4, ChBac5, and mini-ChBac7.5Nb. These chemically synthesized peptides are analogues of natural proline-rich AMPs previously discovered by the authors of the present study in leukocytes of the domestic goat, Capra hircus. These peptides exhibit a high antimicrobial activity, in particular, against antibiotic-resistant gram-negative bacteria. Methods. Minimum inhibitory and minimum bactericidal concentrations of the peptides (MIC and MBC) were determined using the broth microdilution assay followed by subculturing on agar plates. Effects of the AMPs on bacterial cytoplasmic membrane permeability for a chromogenic marker were explored using a genetically modified strain, Escherichia coli ML35p. The effect of bactenecins on bacterial metabolic activity was studied using a resazurin marker. Results. All the studied peptides showed a high in vitro antimicrobial activity against Escherichia coli ML35p and antibiotic-resistant strains, Escherichia coli ESBL and Acinetobacter baumannii, but differed in features of their action on bacterial cells. The used combination of techniques allowed the real-time monitoring of effects of bactenecin at different concentrations (including their MIC and MBC) on the cell membrane barrier function and metabolic activity of bacteria. The differences in effects of these three structurally different bactenecins on the studied microorganisms implied that these peptides at bactericidal concentrations differed in their capability for disintegrating bacterial cell membranes and rate of inhibiting bacterial metabolism. Conclusion. The obtained information will supplement the existing basic concepts on mechanisms involved in effects of proline-rich peptides of the innate immunity. This information will also stimulate biotechnological research aimed at development of new antibiotics for treatment of infectious diseases, such as severe in-hospital infections, caused by antibiotic-resistant strains.

scholarly journals International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women: A 2010 Update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases

2011 ◽  
Vol 52 (5) ◽  
pp. e103-e120 ◽  
Author(s):  
Kalpana Gupta ◽  
Thomas M. Hooton ◽  
Kurt G. Naber ◽  
Björn Wullt ◽  
Richard Colgan ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
European Society ◽  
Uncomplicated Urinary Tract Infection ◽  
Collateral Damage ◽  
Medical Microbiology ◽  
Acute Uncomplicated Cystitis ◽  
American Urological Association ◽  
Uncomplicated Cystitis ◽  
International Experts

Abstract A Panel of International Experts was convened by the Infectious Diseases Society of America (IDSA) in collaboration with the European Society for Microbiology and Infectious Diseases (ESCMID) to update the 1999 Uncomplicated Urinary Tract Infection Guidelines by the IDSA. Co-sponsoring organizations include the American Congress of Obstetricians and Gynecologists, American Urological Association, Association of Medical Microbiology and Infectious Diseases–Canada, and the Society for Academic Emergency Medicine. The focus of this work is treatment of women with acute uncomplicated cystitis and pyelonephritis, diagnoses limited in these guidelines to premenopausal, non-pregnant women with no known urological abnormalities or co-morbidities. The issues of in vitro resistance prevalence and the ecological adverse effects of antimicrobial therapy (collateral damage) were considered as important factors in making optimal treatment choices and thus are reflected in the rankings of recommendations.

The Safety and Antimicrobial Properties of Stabilized Hypochlorous Acid in Acetic Acid Buffer for the Treatment of Acute Wounds—a Human Pilot Study and In Vitro Data

2021 ◽  
pp. 153473462110156
Author(s):  
Ewa A. Burian ◽  
Lubna Sabah ◽  
Klaus Kirketerp-Møller ◽  
Elin Ibstedt ◽  
Magnus M. Fazli ◽  
...  
Keyword(s):  
Pilot Study ◽  
Hypochlorous Acid ◽  
Treatment Time ◽  
Donor Site ◽  
Antimicrobial Properties ◽  
Prolonged Treatment ◽  
Wound Irrigation ◽  
The Mean ◽  
And Performance

Acute wounds may require cleansing to reduce the risk of infection. Stabilized hypochlorous acid in acetic buffer (HOCl + buffer) is a novel wound irrigation solution with antimicrobial properties. We performed a first-in-man, prospective, open-label pilot study to document preliminary safety and performance in the treatment of acute wounds. The study enrolled 12 subjects scheduled for a split-skin graft transplantation, where the donor site was used as a model of an acute wound. The treatment time was 75 s, given on 6 occasions. A total of 7 adverse events were regarded as related to the treatment; all registered as pain during the procedure for 2 subjects. One subject had a wound infection at the donor site. The mean colony-forming unit (CFU) decreased by 41% after the treatment, and the mean epithelialization was 96% on both days 14 (standard deviation [SD] 8%) and 21 (SD 10%). The study provides preliminary support for the safety, well-tolerance, and efficacy of HOCl + buffer for acute wounds. The pain was frequent although resolved quickly. Excellent wound healing and satisfying antimicrobial properties were observed. A subsequent in vitro biofilm study also indicated good antimicrobial activity against Pseudomonas aeruginosa with a 96% mean reduction of CFU, when used for a treatment duration of 15 min ( P < .0001), and a 50% decrease for Staphylococcus aureus ( P = .1010). Future larger studies are needed to evaluate the safety and performance of HOCl + buffer in acute wounds, including the promising antimicrobial effect by prolonged treatment on bacterial biofilms.

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