scholarly journals Risk Factors for the Antibiotic Resistant Gram-Negative Bacilli Associated Infections in Burn Patients and the In-Vitro Susceptibility of Colistin

2020 ◽  
Vol 15 (3) ◽  
Author(s):  
Mojtaba Varshochi ◽  
Alka Hasani ◽  
Parinaz Pour Shahverdi ◽  
Fateme Ravanbakhsh Ghavghani ◽  
Somaieh Matin
Keyword(s):  
Risk Factors ◽  
Infectious Complications ◽  
Test Methods ◽  
Burn Patients ◽  
In Vitro Susceptibility ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Burn Unit ◽  
Microbial Infections

Background: Burns patients are predisposed to infectious complications. Amongst microbial infections, Gram-negative bacilli are the most prevalent bacteria in the burn units. Objectives: The current study aimed to identify the risk factors associated with antibiotic-resistant Gram-negative bacilli in hospitalized burn patients and determine the in-vitro susceptibility of these organisms to colistin. Methods: Two hundred burn patients hospitalized in the burn unit and ICU burn ward were allocated to two groups (each with 100 patients) of patients with antibiotic-resistant Gram-negative bacilli infections and the other with antibiotic susceptible Gram-negative bacilli associated infections. The susceptibility of Gram-negative bacilli was done towards various antibacterial agents by the Kirby-Bauer method. Susceptibility of colistin was performed using both E-test and disc diffusion methods. Results: The history of antibiotic usage, length of ICU stay, mechanical ventilation, and catheter usage were the most important risk factors for infections associated with antibiotic-resistant Gram-negative bacilli. Pseudomonas aeruginosa and Acinetobacter baumannii were the most prevalent bacteria in the burn unit. Only one A. baumannii isolate was found resistant toward colistin by both disk diffusion and E-test methods. Conclusions: Burn patients are prone to infections, and Gram-negative bacilli predominates in patients harboring risk factors. These findings influence the choice of traditional therapeutic regimens in such patients. Colistin served as an appropriate antibiotic choice.

scholarly journals Epidemiology of Inappropriate Empiric Antibiotic Therapy for Bacteremia Based on Discordant In vitro Susceptibilities: Risk factors and Taxon-level Variation in Burden and Outcome in 156 US hospitals, 2000–2014

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S13-S14
Author(s):  
Sameer S Kadri ◽  
Yi Ling Lai ◽  
Emily Ricotta ◽  
Jeffrey Strich ◽  
Ahmed Babiker ◽  
...  
Keyword(s):  
Risk Factors ◽  
Antibiotic Therapy ◽  
Empiric Antibiotic Therapy ◽  
In Vitro Susceptibility ◽  
Gram Negative ◽  
Risk Of Death ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
Empiric Antibiotic

Abstract Background Discordance between in vitro susceptibility and empiric antibiotic therapy is inextricably linked to antibiotic resistance and decreased survival in bloodstream infections (BSI). However, its prevalence, patient- and hospital-level risk factors, and impact on outcome in a large cohort and across different pathogens remain unclear. Methods We examined in vitro susceptibility interpretations for bacterial BSI and corresponding antibiotic therapy among inpatient encounters across 156 hospitals from 2000 to 2014 in the Cerner Healthfacts database. Discordance was defined as nonsusceptibility to initial therapy administered from 2 days before pathogen isolation to 1 day before final susceptibility reporting. Discordance prevalence was compared across taxa; risk factors and its association with in-hospital mortality were evaluated by logistic regression. Adjusted odds ratios (aOR) were estimated for pathogen-, patient- and facility-level factors. Results Of 33,161 unique encounters with BSIs, 4,219 (13%) at 123 hospitals met criteria for discordant antibiotic therapy, ranging from 3% for pneumococci to 55% for E. faecium. Discordance was higher in recent years (2010–2014 vs. 2005–2009) and was associated with older age, lower baseline SOFA score, urinary (vs. abdominal) source and hospital-onset BSI, as well as ≥500-bed, Midwestern, non-teaching, and rural hospitals. Discordant antibiotic therapy increased the risk of death [aOR = 1.3 [95% CI 1.1–1.4]). Among Gram-negative taxa, discordant therapy increased risk of mortality associated with Enterobacteriaceae (aOR = 1.3 [1.0–1.6]) and non-fermenters (aOR = 1.7 [1.1–2.5]). Among Gram-positive taxa, risk of mortality from discordant therapy was significantly higher for S. aureus (aOR = 1.3 [1.1–1.6]) but unchanged for streptococcal or enterococcal BSIs. Conclusion The prevalence of discordant antibiotic therapy displayed extensive taxon-level variability and was associated with patient and institutional factors. Discordance detrimentally impacted survival in Gram-negative and S. aureus BSIs. Understanding reasons behind observed differences in discordance risk and their impact on outcomes could inform stewardship efforts and guidelines for empiric therapy in sepsis. Disclosures All authors: No reported disclosures.

Systematic analysis and integrative discovery of active-site subpocket-specific dehydroquinate synthase inhibitors combating antibiotic-resistant Staphylococcus aureus infection

2018 ◽  
Vol 16 (06) ◽  
pp. 1850027
Author(s):  
Quanfeng Liu ◽  
Liping Li ◽  
Fei Xu
Keyword(s):  
Staphylococcus Aureus ◽  
Active Site ◽  
Shikimate Pathway ◽  
In Vitro Susceptibility ◽  
Systematic Analysis ◽  
Antibiotic Resistant ◽  
Enzyme Active Site ◽  
Specific Inhibitors ◽  
Dehydroquinate Synthase

Shikimate pathway plays an essential role in the biosynthesis of aromatic amino acids in various plants and bacteria, which consists of seven key enzymes and they are all attractive targets for antibacterial agent development due to their absence in humans. The Staphylococcus aureus dehydroquinate synthase (SaDHQS) is involved in the second step of shikimate pathway, which catalyzes the NAD[Formula: see text]-dependent conversion of 3-deoxy-D-arabino-heptulosonate-7-phosphate to dehydroquinate via multiple steps. The enzyme active site can be characterized by two spatially separated subpockets 1 and 2, which represent the reaction center of substrate adduct with NAD[Formula: see text] nicotinamide moiety and the assistant binding site of NAD[Formula: see text] adenine moiety, respectively. In silico virtual screening is performed against a biogenic compound library to discover SaDHQS subpocket-specific inhibitors, which were then tested against both antibiotic-sensitive and antibiotic-resistant S. aureus strains by using in vitro susceptibility test. The activity profile of hit compounds has no considerable difference between the antibiotic-sensitive and -resistant strains. The subpocket 1-specific inhibitors exhibit a generally higher activity than subpocket 2-specific inhibitors, and they also hold a strong selectivity between their cognate and noncognate subpockets. Dynamics and energetics analyses reveal that the SaDHQS active site prefers to interact with amphipathic and polar inhibitors by forming multiple hydrogen bonds and van der Waals packing at the complex interfaces of the two subpockets with their cognate inhibitors.

26 Clogged Feeding Tubes: Why Does It Matter?

2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S22-S23
Author(s):  
Sarah Zavala ◽  
Ashley Wang ◽  
Cheryl W Zhang ◽  
Jennifer M Larson ◽  
Yuk Ming Liu
Keyword(s):  
Risk Factors ◽  
Length Of Stay ◽  
Nutritional Support ◽  
Total Body Surface Area ◽  
Tube Feeding ◽  
Feeding Tube ◽  
Admission Diagnosis ◽  
Burn Patients ◽  
Feeding Tubes ◽  
Burn Unit

Abstract Introduction Many patients treated on a burn unit require tube feeding as their primary caloric source or as supplemental feeding due to their injuries. Burn patients specifically require higher caloric intake due to the hypermetabolic state of burn injuries. Inadequate nutritional support contributes to longer ICU stays and higher mortality. Clogged feeding tubes reduce nutrition provided due to temporary discontinuation of feeding. The objective of this study was to identify risk factors for the incidence of tube clogging. Methods This was a single-center retrospective chart review of all patients admitted to an American Burn Association-verified Burn Unit between August 2017 and October 2019 who received tube feeds during their admission. Data collected included baseline demographics, clinical outcomes, and details about tube feed formulations, number of clogs, and details leading up to the clog. Baseline demographics were compared using descriptive statistics. Nominal data was compared using Chi-square test. Continuous data was analyzed using student’s t-test or Mann-Whitney U test. Results A total of 170 patients were included; admission diagnoses included burn (97), soft tissue infections (29), SJS/TEN (11), and others (33). At least one clogged feeding tube was experienced by 51 patients and some experienced up to seven separate clogs. SJS/TEN patients were less likely to experience a clog (9.2 vs 0%, p = 0.035) and frostbite patients were more likely to experience a clog (0 vs 5.9%, p = 0.026). Burn mechanism did not affect incidence of tube feed clog, but patients with larger total body surface area (TBSA) burned were more likely to have a clog (15.55 vs 25.03%, p = 0.004). It was a median of 12 days until the first clog occurred (IQR 7.8–17.3). Two tube feed formulas demonstrated an increased likelihood of clog: a renal formulation (16.8 vs 33.3%, p = 0.017) and a polymeric concentrated product (5.0 vs 17.6%, p = 0.008). Both products have a high viscosity. Patients who experienced a clog had a longer length of stay (21.5 vs 44.0 days, p = 0.001). Conclusions This study identified several risk factors associated with higher incidence of clogged feeding tube in the burn unit including tube feed formulation and viscosity, admission diagnosis, and larger TBSA in burn patients. This study also confirms that clogged feeding tubes, and the resultant insufficient nutritional support, may contribute to an increased length of stay.

scholarly journals 519. Multidrug-resistant Gram-Negative Bacteremia in Pediatric Patients: Is It Time to Change to Empiric Meropenem?

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S250-S250
Author(s):  
Kanokporn Mongkolrattanothai ◽  
Leslie Stach ◽  
Regina Orbach
Keyword(s):  
Antimicrobial Agents ◽  
Pediatric Patients ◽  
Multidrug Resistant ◽  
Suspected Sepsis ◽  
In Vitro Susceptibility ◽  
Gram Negative ◽  
Gram Negative Bacteremia ◽  
Delayed Initiation ◽  
Poor Outcomes

Abstract Background The rise of antimicrobial resistance among gram-negative (GN) pathogens has been dramatic nationally. Delayed initiation of active antimicrobial agents has been associated with poor outcomes. We aimed at evaluating the prevalence and treatment of multi-drug-resistant gram-negative (MDR-GN) bacteremia in our pediatric patients. Methods All episodes of GN bacteremia from 2017–2018 at our institution were retrospectively reviewed. GN defined as MDR in our study were carbapenem-resistant organisms (CRO), extended-spectrum β-lactamase (ESBL) producers, and GN that were resistant to cefepime and ≥2 classes of non-cephalosporin antimicrobial agents. Stenotrophomonas maltophilia was excluded. Ineffective empirical treatment (IET) is defined as an initial antibiotic regimen that is not active against the identified pathogen[s] based on in vitro susceptibility testing results. Results A total of 292 episodes of GN bacteremia were identified and 6 S. maltophilia were excluded. Of these, 29 bacteremic episodes in 26 patients were caused by MDR-GN organisms including 18 ESBL, 7 CRO, 1 ESBL and CRO, 3 non-ESBL/non-CRO cefepime-resistant MDR-GN. None of the CRO had carbapenemase genes detected. However, there was a patient with multiple sites of infection simultaneously with non-NDM CR Acinetobacter bacteremia and NDM-mediated CR-Klebsiella ventriculitis. The annual rate of MDR-GN bacteremia increased from 8% in 2017 to 12% in 2018. Almost half (48%) of episodes were community onset. Among these, all but one had underlying medical conditions with hospital exposure and most patients had central venous devices at the time of infection. 52% (15/29) episodes of MDR-GN bacteremia had IET. Despite IET, 47% (7/15) had negative blood cultures prior to initiation of effective therapy (6 ESBL and 1 P. aeruginosa). Various antibiotic regimens were used for CRO therapy as shown in Table 1. Conclusion In our institution, MDR-GN infection is increasing. As such, empiric meropenem is currently recommended in BMT or neutropenic patients with suspected sepsis. However, empiric meropenem must be used judiciously as its widely use will lead to more selection of MDR pathogens. It is essential to continue monitoring of these MDR-GN to guide appropriate empiric regimens. Disclosures All authors: No reported disclosures.

scholarly journals Risk factors for thromboembolism in burn patients admitted to the burn unit at King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia

2019 ◽  
Vol 40 (10) ◽  
pp. 1027-1031
Author(s):  
Thamer Althunayan ◽  
Saad AlQarni ◽  
Waleed Mohsenh ◽  
Ahmed Alkhalifah ◽  
Abdullmajeed Alsadi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Saudi Arabia ◽  
Burn Patients ◽  
Kingdom Of Saudi Arabia ◽  
Burn Unit ◽  
Medical City

scholarly journals TSPphg Lysin from the Extremophilic Thermus Bacteriophage TSP4 as a Potential Antimicrobial Agent against Both Gram-Negative and Gram-Positive Pathogenic Bacteria

Viruses ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 192 ◽  
Author(s):  
Feng Wang ◽  
Xinyu Ji ◽  
Qiupeng Li ◽  
Guanling Zhang ◽  
Jiani Peng ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Infection Model ◽  
Bacterial Cells ◽  
Skin Damage ◽  
Gram Positive ◽  
Antibiotic Resistant ◽  
Gram Negative

New strategies against antibiotic-resistant bacterial pathogens are urgently needed but are not within reach. Here, we present in vitro and in vivo antimicrobial activity of TSPphg, a novel phage lysin identified from extremophilic Thermus phage TSP4 by sequencing its whole genome. By breaking down the bacterial cells, TSPphg is able to cause bacteria destruction and has shown bactericidal activity against both Gram-negative and Gram-positive pathogenic bacteria, especially antibiotic-resistant strains of Klebsiella pneumoniae, in which the complete elimination and highest reduction in bacterial counts by greater than 6 logs were observed upon 50 μg/mL TSPphg treatment at 37 °C for 1 h. A murine skin infection model further confirmed the in vivo efficacy of TSPphg in removing a highly dangerous and multidrug-resistant Staphylococcus aureus from skin damage and in accelerating wound closure. Together, our findings may offer a therapeutic alternative to help fight bacterial infections in the current age of mounting antibiotic resistance, and to shed light on bacteriophage-based strategies to develop novel anti-infectives.

scholarly journals Ceftazidime/Avibactam: Who Says You Can’t Teach an Old Drug New Tricks?

2016 ◽  
Vol 19 (4) ◽  
pp. 448 ◽  
Author(s):  
Katie E. Barber ◽  
Jessica K. Ortwine ◽  
Ronda L Akins
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
The United States ◽  
Phase Iii ◽  
In Vitro Susceptibility ◽  
Gram Negative ◽  
Tract Infections ◽  
Abdominal Infections

Purpose: Gram-negative resistance continues to rise with treatment options becoming more limited. Ceftazidime/avibactam was recently approved in the United States and Europe, which combines an established third-generation cephalosporin with a new, unique, non-β-lactam β-lactamase inhibitor. This review conducts a thorough examination of structure, pharmacology, spectrum of activity, pharmacokinetics/pharmacodynamics, in vitro and clinical efficacy and safety/tolerability of ceftazidime/avibactam, as well as detailed future directions for the agent. Methods: Pubmed and clinicaltrials.gov searches, as well as abstracts from the 2015 Interscience Conference on Antimicrobial Agents and Chemotherapy/International Society of Chemotherapy (ICAAC/ICC) and ID Week meetings and the 2016 American Society of Microbiology Microbe meeting, were conducted from January 2004 – September 2016. Relevant search terms included ceftazidime, ceftazidime/avibactam, avibactam, NXL104 and AVE1330A. The US package insert for ceftazidime/avibactam (02/2015) and European public assessment report (06/2016) were also reviewed. Results: In vitro susceptibility for ceftazidime/avibactam displayed potent activity against many Enterobacteriaceae including extended-spectrum-β-lactamase (ESBL) and carbapenemase-producing strains, as well as Pseudomonas aeruginosa. Phase II clinical trials utilized for approval demonstrated comparable safety and efficacy to imipenem/cilistatin for treatment of complicated urinary tract infections (70.4% vs. 71.4%) and combined with metronidazole compared to meropenem in complicated intra-abdominal infections (91.2% vs 93.4%). Phase III data displayed non-inferior efficacy of ceftazidime/avibactam compared to doripenem for complicated urinary tract infections (70.2% vs 66.2%) and combined with metronidazole compared to meropenem in complicated intra-abdominal infections (82.5% vs 84.9%), as well as comparable safety. Ceftazidime/avibactam was well-tolerated but does require renal adjustments. Additionally, 3 case series and a single case report have demonstrated the potential for ceftazidime/avibactam against multidrug resistant organisms for compassionate use or failure after previous therapy. Conclusion: By adding avibactam to ceftazidime, clinicians’ antimicrobial armamentarium is expanded, potentially increasing the ability to combat multi-drug resistant gram-negative pathogens, particularly ESBL and carbapenemase-producing organisms, as well as Pseudomonas aeruginosa. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Risk Factors for Bloodstream Infections due to Multidrug-resistant Gram-negative Non-fermenting Bacteria in a Burn Unit

2008 ◽  
Vol 12 ◽  
pp. S39-S40
Author(s):  
Süheyla Senger ◽  
Funda Timurkaynak ◽  
Hande Arslan ◽  
Turhan Togan ◽  
Özgür Başaran ◽  
...  
Keyword(s):  
Risk Factors ◽  
Bloodstream Infections ◽  
Multidrug Resistant ◽  
Gram Negative ◽  
Burn Unit ◽  
Fermenting Bacteria
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