TRPV1+ neurons alter Staphylococcus aureus skin infection outcomes by affecting macrophage polarization and neutrophil recruitment.

BACKGROUND: The interaction between the nervous system and the immune system can affect the outcome of a bacterial infection. Staphylococcus aureus skin infection is a common infectious disease, and elucidating the relationship between the nervous system and immune system may help to improve treatment strategies. RESULTS: In this study, we found that the local release of calcitonin gene-related peptide (CGRP) increased during S. aureus skin infection, and S. aureus could promote the release of CGRP from transient receptor potential cation channel subfamily V member 1 (TRPV1+) neurons in vitro. The existence of TRPV1+ neurons inhibited the recruitment of neutrophils to the infected region and regulated the polarization of macrophages toward M2 while inhibiting polarization toward M1. This reduces the level of inflammation in the infected area, which aggravates the local infection. Furthermore, this study demonstrates that TRPV1 may be a target for the treatment of S. aureus skin infections and that botulinum neurotoxin A (BoNT/A) and BIBN4096 may reverse the inhibited inflammatory effect of CGRP, making them potential therapeutics for the treatment of skin infection in S. aureus. CONCLUSIONS: In S. aureus skin infection, TRPV1+ neurons inhibit neutrophil recruitment and regulate macrophage polarization by releasing CGRP. BoNT/A and BIBN4096 may be potential therapeutic agents for S. aureus skin infection.

Genetic and Functional Analysis of the pks Gene in Clinical Klebsiella pneumoniae Isolates.

The pks gene cluster encodes colibactin, which can cause DNA damage and enhance the virulence in Escherichia coli. However, the role of the pks gene in Klebsiella pneumoniae has not been fully discussed. The aim of this study was to analyze the relationship between the pks gene cluster and virulence factors, as well as to assess antibiotic resistance and biofilm formation capacity in clinical isolates of Klebsiella pneumoniae. Thirty-eight of 95 clinical K. pneumoniae strains were pks positive. pks-positive strains usually infected emergency department patients, and pks-negative strains often infected hospitalized patients. The positive rates of K1 capsular serotype and hypervirulence genes (peg-344, rmpA, rmpA2, iucA, and iroB) were significantly higher in the pks-positive isolates than the pks-negative isolates (P < 0.05). The biofilm formation ability of pks-positive isolates was stronger than that of pks-negative isolates. Antibacterial drug susceptibility test showed the resistance of pks-positive isolates was weaker than that of pks-negative isolates. In conclusion, patients with pks-positive K. pneumoniae infection might have worse treatment outcomes and prognosis. pks-positive K. pneumoniae might have stronger virulence and pathogenicity. Clinical infection with pks-positive K. pneumoniae needs further attention. IMPORTANCE The infection rate with pks-positive K. pneumoniae has been increasing in recent years. Two previous surveys in Taiwan reported 25.6% pks gene islands and 16.7% pks-positive K. pneumoniae strains in bloodstream infections, and Chinese scholars also did a survey of K. pneumoniae bloodstream infections in Changsha, China, and found 26.8% pks-positive K. pneumoniae. In addition, it was found that the pks gene cluster might encode colibactin, which could be related to the virulence of K. pneumoniae. Studies confirmed that the prevalence of colibactin-producing K. pneumoniae was increasing. It is necessary to consider the clear relationship between the pks gene cluster and high pathogenicity in K. pneumoniae.

Diagnosis of Coxiella burnetii Prosthetic Joint Infection Using mNGS and ptNGS: A Case Report and Literature Review.

BACKGROUND: Coxiella burnetii (C. burnetii) is the causative agent of Q fever and is found worldwide; however, prosthetic joint infections caused by C. burnetii are rarely seen. Because of advances in molecular diagnostic techniques, prosthetic joint infection (PJI) caused by C. burnetii can now be diagnosed. CASE PRESENTATION: A 77-year-old male who had undergone total knee arthroplasty had a displaced prosthesis and periprosthetic osteolysis; he had no obvious signs of infection, and microbiological culture was negative. However, C. burnetii was detected by metagenomic next-generation sequencing (mNGS) and pathogen-targeted next-generation sequencing (ptNGS). Finally, polymerase chain reaction (PCR) confirmed the diagnosis of C. burnetii prosthetic joint infection (PJI). After revision surgery (one-stage revision) and oral antibiotics (doxycycline and moxifloxacin hydrochloride), the patient's symptoms disappeared, and he regained the ability to walk. During the 6-month follow-up, the patient's knee showed no signs of swelling, pain or the recurrence of infection, and he experienced no significant complications. We also present a review of the literature for other cases of C. burnetii PJI. CONCLUSIONS: The symptoms of C. burnetii PJI may be different from those of Q fever, which may lead to misdiagnosis. mNGS and ptNGS may be helpful for the identification of C. burnetii. Once the diagnosis of C. burnetii PJI is confirmed, doxycycline in combination with a fluoroquinolone can be effectively administered after revision surgery.

Prevalence and predictors of polypharmacy prescription among type 2 diabetes patients at a tertiary care department in Ningbo, China: A retrospective database study.

OBJECTIVES: To determine the prevalence of polypharmacy prescription among type 2 diabetes (T2DM) patients at a tertiary care department in Ningbo, China, and to determine factors that independently predict this polypharmacy prescription. METHODS: A retrospective cross-sectional study was conducted using an existing computerised medical records database. This database was screened from 2012 to 2017 for adult patients with T2DM and parameters like prescribed medicines and socio-demographic, behavioural and other medical information. Polypharmacy prescription was defined as the simultaneous prescription of ≥5 medicines by the clinician at the time of discharge for daily usage by the patient as part of his/her long-term treatment plan. RESULTS: The study inclusion criteria were satisfied by 3370 T2DM patients. Over a 5-year period, 72.2% (n = 2432) of T2DM patients were prescribed polypharmacy. On an average, eight medicines were prescribed to them. The odds of polypharmacy prescription increased with patients' age (18-39 years: 1; 40-59 years: OR 1.86, 95% CI 1.28-2.71; and ≥60 years: 2.42, 1.65-3.55), duration of T2DM (≤1 year: 1; >5-10 years: 1.70, 1.10-2.62; and >10 years: 2.55, 1.68-3.89), and length of hospital stay (≤5 days: 1; >5-10 days: 2.43, 1.86-3.17; and >10 days: 2.99, 2.24-3.99), and were higher in those with poor blood glucose level (2.09, 1.67-2.62) and with comorbidities like other endocrine, nutritional and metabolic diseases (2.24, 1.76-2.85), circulatory system diseases (4.35, 3.62-5.23), skin and subcutaneous tissue diseases (1.64, 1.04-2.59), and musculoskeletal system and connective tissue diseases (1.61, 1.27-2.03). The odds of polypharmacy prescription were lower in those with comorbidities like neoplasms (0.51, 0.36-0.70) and during pregnancy, childbirth and the puerperium (0.06, 0.01-0.49). CONCLUSIONS: Around three fourth of T2DM patients at the tertiary care department were prescribed polypharmacy, and the predictors were identified. The study findings could be taken into consideration in future interventional studies aimed at supporting medicines optimisation (and deprescribing) among these patients.

Dietary and physical activity of adult patients with type 2 diabetes in Zhejiang province of eastern China: Data from a cross-sectional study.

AIMS/INTRODUCTION: Lifestyle management helps improve the clinical outcome of patients with type 2 diabetes. The present study aimed to obtain lifestyle data on the dietary and physical activity of adult type 2 diabetes patients in Zhejiang province of eastern China for better patient education and improvement of clinical management. MATERIALS AND METHODS: A cross-sectional survey of 607 adult type 2 diabetes patients was carried out in 12 hospitals within eight cities of Zhejiang province. Data were collected for sex, age, basic physical measurement (blood pressure, height, weight, waist circumference and hip circumference), dietary favor and habit (vegetarian diets vs meat diets, preference of salty or light flavors), detailed dietary intake (24-h recall method), as well as the weekly physical activity. RESULTS: The mean age of the patients in the analysis was 56.39 ± 12.29 years, and 38.71% of the patients had higher levels of body mass index than recommended. The average daily total energy intake was 1887.71 ± 575.10 kcal. The percentage of calories from carbohydrate, protein and fat were 61.36 ± 11.59%, 13.29 ± 3.37% and 25.35 ± 11.16%, respectively. For physical activity, the patients generally spent most of their daily time sitting and sleeping, and the time for moderate vigorous activity was limited. CONCLUSIONS: Adult patients with type 2 diabetes in Zhejiang province have a relatively high carbohydrate and low protein diet, with very limited physical activity. Patient education to achieve a better lifestyle intervention needs to improve in this region.