Treatment of Staphylococcus aureus infections continues to be a challenge due to antimicrobial resistance. Endogenous antimicrobial peptides may offer a new option for treating S. aureus infections but several factors limit their clinical utility. Herein, we studied the activity of the antimicrobial peptide LL-37 and two truncated derivatives, LL-13 and LL-17 alone and in combination with vancomycin against a range of drug-resistant S. aureus strains including methicillin resistant S. aureus (MRSA) and vancomycin resistant S. aureus (VRSA) strains in vitro. When used with vancomycin, LL-13 and LL-17 displayed synergy against VRSA and showed the ability to restore sensitivity to vancomycin after pretreatment. In addition, LL-13 and LL-17 showed a strong ability to inhibit S. aureus biofilm production. LL-37 derivatives may be useful in treating infections that are resistant to vancomycin or in scenarios where biofilm formation is a concern.
ObjectiveThe aim of this study was to compare the incidence of skin and soft tissue infections (SSTIs) across healthcare settings and analyze direct healthcare expenditures related to SSTIs in 2000 and 2012 in the United States.MethodsWe performed a retrospective, cross-sectional analysis of nationally representative data from the Medical Expenditure Panel Surveys. Population-based incidence rates were examined for all healthcare settings that include inpatient visits, emergency department visits and ambulatory visits for SSTIs. The direct costs of healthcare services utilization were reported. Population-based prescribing rates for each antimicrobial class during ambulatory visits were compared.ResultsA total of 2.4 million patients experienced an SSTI in 2000 compared to 3.3 million in 2012 (40% increase). From 2000 to 2012, the incidence of patients with at least one hospital visit for SSTIs increased 22%, ambulatory care visits increased 30%, and emergency department visits increased 40%. The incidence of SSTIs in children and adolescents declined 50% (from 150 to 76 per 10,000 person; RR = 0.51, 95% CI: 0.38–0.67; p<0.001) whereas SSTIs in older adults (> 65 years of age) increased almost 2-fold (from 67 to 130 per 10,000 person; RR = 1.94, 95% CI: 1.44–2.61; p<0.001). The annual incidence of SSTI in adults did not change significantly from 2000 to 2012 (from 84 to 81 per 10,000 person; RR = 0.96, 95% CI: 0.71–1.31; p = 0.41). The total estimated direct healthcare costs of SSTIs increased 3-fold from $4.8 billion in 2000 to $15.0 billion in 2012, largely driven by an 8-fold increase in ambulatory expenditures for SSTIs. Total population-based antimicrobial prescription rates for SSTIs increased 4-fold from 2000 to 2012 (from 59.5 to 250.4 per 10,000 person).ConclusionsThe highest healthcare utilization for SSTI treatment occurred in the ambulatory care setting and also accounted for the largest increase in overall direct expenditures from 2000 to 2012.
BackgroundCarbapenem-resistant Enterobacterales (CRE) pose a significant global public health threat. Resistance among CRE is particularly complex, owing to numerous possible resistance mechanisms and broad definitions. We aimed to characterize the clinical and molecular profiles of CRE in the South Texas region.Materials and methodsWe compared the clinical, genotypic, and phenotypic profiles of carbapenemase producing Enterobacterales (CPE) with those of non-carbapenemase producers (NCPE) isolated from South Texas, United States between 2011 and 2019. Molecular characteristics and resistance mechanisms were analyzed using whole-genome sequences.ResultsThe majority (59%) of the CRE isolates were NCPE while 41% of isolates harbored carbapenemases, predmonantly blaKPC-type. The most common CPE was Klebsiella pneumoniae while majority of Enterobacter cloacae and Escherichia coli were NCPE Among K. pneumoniae, the clonal group 307 has emerged as a predmoninant group and was associated with as many CRE infections as the previous common clonal group 258. Patients with NCPE compared to CPE infections were associated with higher antimicrobial exposure prior to culture collection (days of therapy, 795 vs. 242; p < 0.001) and emergency department visits within past 90 days (22% vs. 4%; p = 0.011). The all cause 30-day mortality was 21%.ConclusionsThis study highlights the diversity of resistance mechanisms underlying CRE in South Texas, with 59% not harboring a carbapenemase. Individuals with NCPE infections were more likely to have had prior antimicrobial therapy and emergency department visits compared to those with CPE. Identification and distinction of these mechanisms by rapid identification of species and carbapenemase would allow for optimal treatment and infection control efforts.
Indwelling medical devices have become a major source of nosocomial infections, especially Pseudomonas aeruginosa infections, which remain the most common cause of ventilator-associated pneumonia (VAP) in neonates and children. Using medical grade polyvinyl chloride endotracheal tubes (ETTs), the activity of tobramycin and polymyxin E was quantified in a simulated prevention and treatment static time-kill model using biofilm-forming P. aeruginosa. The model simulated three clinical conditions: (i) planktonic bacteria grown in the presence of antibiotics (tobramycin and polymyxin E) without ETTs, (ii) planktonic bacteria grown in the presence of P. aeruginosa, antibiotic, and ETTs (simulating prevention), and (iii) a 24-h-formed P. aeruginosa biofilm grown on ETTs prior to antibiotic exposure (simulating treatment). In the model simulating "prevention" (conditions 1 and 2 above), tobramycin alone or in combination with polymyxin E was more bactericidal than polymyxin E alone at 24 h using a concentration of greater than 2 times the MIC. However, after a 24-h-old biofilm was allowed to form on the ETTs, neither monotherapy nor combination therapy over 24 h exhibited bactericidal or bacteriostatic effects. Against the same pathogens, tobramycin and polymyxin E, alone or in combination, exhibited bactericidal activity prior to biofilm attachment to the ETTs; however, no activity was observed once biofilm formed on ETTs. These findings support surveillance culturing to identify pathogens for a rapid and targeted approach to therapy, especially when P. aeruginosa is a potential pathogen. Indwelling medical devices are a major source of nosocomial infections. In particular, patients requiring mechanical ventilation (intubation with an endotracheal tube [ETT]) face a high probability of contracting one of the most prevalent nosocomial infections, ventilator-associated pneumonia (VAP) (1-3). Neonatal and pediatric populations are at especially high risk for VAP because the current standard of care involves prolonged intubation without ETT exchange or tracheostomy, both common practice in adult patients. In neonates and infants, the inner diameter of the ETT is often 2.5 to 3.5 mm (the size of a thin straw), which complicates suctioning of secretions and confounds attempts to maintain patency. Despite aggressive bedside hygiene, Pseudomonas aeruginosa remains one of the most common causes of VAP in intubated children (2,4,5).P. aeruginosa, often found on indwelling devices such as ETTs, forms a biofilm which serves as an ideal environment for antibiotic resistance, making VAP difficult to treat (6, 7). Biofilm on ETTs is considered to be a reservoir for infecting pathogens derived from oropharyngeal flora and gastric microaspiration and is highly correlated with lower airway infection and subsequent VAP (8-11). To date, few side-by-side studies have compared killing activity (defined as 99.9% kill) of tobramycin to that of polymyxin E against P. aeruginosa, especially in the context of ETT biofilm and VAP (12-15). The eff...
Background Diabetic foot infections (DFIs) constitute the most common cause for diabetes-related hospitalization and lower extremity amputations. Current diagnostic methods are slow and in some cases do not detect all potential pathogens. Metagenomics sequencing has the potential to merge rapidity and comprehensive information about causative pathogens in DFIs. The aim of this study was to evaluate the potential of metagenomics strategies for DFIs.Methods Thirty tissue specimens from patients with neuropathic plantar DFIs were analyzed. Specimens were processed using the Molzym Molysis five basic kit to deplete human cells. Microbial DNA was extracted using the Qiagen DNeasy PowerSoil kit. Microbial 16s rRNA was conducted on the Illumina MiSeq instrument. Shotgun metagenomics was conducted using nanopore sequencing for seven samples. Libraries were prepared using the rapid low input PCR library preparation kit (SQK-RI001) and sequenced on a MinION using R9.4 (FLO-MIN 106) flow cells. Real-time identification of pathogens and antimicrobial resistance determinants (ARDs) were conducted using EPI2ME’s WIMP and ARMA applications, respectively.ResultsOverall, the cohort characteristics included: 60% male, mean age 49 years, mean HgA1c 10.2%, and median PEDIS score 3. 16s sequencing identified reads belonging to bacteria isolated by culture, but also identified additional anaerobic pathogens in 70% of the specimens. Nanopore sequencing generated an average of 16.4 Mbp and an average read length of 1620–2700 bp. Shotgun metagenomics correctly detected the pathogens found in culture and in 16s rRNA sequencing; the time to accurate classification thresholds was completed in <1 hour. In two samples, several pathogens including anaerobes and fungi were identified that were not isolated by standard culture methods. The resistome included a range of 8–32 ARDs per sample. Furthermore, the resistomes were highly predictive (sensitivity 98% and specificity 88%) for antimicrobial resistance phenotypes detected by standard susceptibility testing.Conclusion Metagenomics-based sequencing has the potential to offer a rapid (<6 hours sample to result time) and accurate strategy for detecting and identifying pathogens and ARDs involved in DFIs.Disclosures All authors: No reported disclosures.
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