Use of RT-PCR in conjunction with a respiratory pathogen assay to concurrently determine the prevalence of bacteria and SARS-CoV-2 from the nasopharynx of outpatients.

Introduction: COVID-19 has emerged as a highly contagious and debilitating disease caused by the SARS-CoV-2 virus and has claimed the lives of over 7.7 million people worldwide. Bacterial co-infections are one of many co-morbidities that have been suggested to impact the outcome of COVID-19 in patients. The goals of this study are to elucidate the presence of bacteria in the nasopharynx of SARS-CoV-2 positive and negative patients and to describe demographic categories that may be associated with the detection of these organisms during one of the initial waves of the COVID-19 pandemic. Methods: To this end, we investigated SARS-CoV-2 and bacterial co-detection from outpatient RT-PCR testing in Texas. Results: The results indicate that Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae were the most frequently detected bacteria in both SARS-CoV-2 positive and SARS-CoV-2 negative patients and that these bacteria were present in these two patient populations at similar proportions. We also detected Staphylococcus aureus in a significantly larger proportion of males relative to females and people under 65 years of age relative to those 65 and over. Finally, we observed that SARS-CoV-2 was more commonly detected in Hispanics compared to non-Hispanics; however, low disclosure rates make volunteer bias a concern when interpreting the effects of demographic variables. Discussion: This study describes the bacteria present in the nasopharynx of SARS-CoV-2 positive and negative patients, highlights associations between patient demographics and SARS-CoV-2 as well as bacterial co-detection. In addition, this study highlights RT-PCR based molecular testing as a tool to detect bacteria simultaneously when SARS-CoV-2 tests are performed.

Predominance of Non-carbapenemase Producing Carbapenem-Resistant Enterobacterales in South Texas.

BACKGROUND: Carbapenem-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 METHODS: We 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. RESULTS: The majority (59%) of the CRE isolates were NCPE while 41% of isolates harbored carbapenemases, predmonantly bla KPC-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%. CONCLUSIONS: This 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.

Age-based health and economic burden of skin and soft tissue infections in the United States, 2000 and 2012.

OBJECTIVE: The 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. METHODS: We 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. RESULTS: A 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). CONCLUSIONS: The 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.

Evaluation of LL-37 antimicrobial peptide derivatives alone and in combination with vancomycin against S. aureus.

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.

Activities of tobramycin and polymyxin E against Pseudomonas aeruginosa biofilm-coated medical grade endotracheal tubes.

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.