BackgroundPseudomonas aeruginosa is a common pathogen in chronic respiratory tract infections. It typically makes a biofilm, which makes treatment of these infections difficult. In this study, we investigated the inhibitory effects of N-acetylcysteine (NAC) on biofilms produced by P. aeruginosa.ResultsWe found that minimum inhibitory concentrations (MICs) of NAC for most isolates of P. aeruginosa were 10 to 40 mg/ml, the combination of NAC and ciprofloxacin (CIP) demonstrated either synergy (50%) or no interaction (50%) against the P. aeruginosa strains. NAC at 0.5 mg/ml could detach mature P. aeruginosa biofilms. Disruption was proportional to NAC concentrations, and biofilms were completely disrupted at 10 mg/ml NAC. Analysis using COMSTAT software also showed that PAO1 biofilm biomass decreased and its heterogeneity increased as NAC concentration increased. NAC and ciprofloxacin showed significant killing of P. aeruginosa in biofilms at 2.5 mg/ml and > 2 MIC, respectively (p < 0.01). NAC-ciprofloxacin combinations consistently decreased viable biofilm-associated bacteria relative to the control; this combination was synergistic at NAC of 0.5 mg/ml and CIP at 1/2MIC (p < 0.01). Extracellular polysaccharides (EPS) production by P. aeruginosa also decreased by 27.64% and 44.59% at NAC concentrations of 0.5 mg/ml and 1 mg/ml.ConclusionsNAC has anti-bacterial properties against P. aeruginosa and may detach P. aeruginosa biofilms. Use of NAC may be a new strategy for the treatment of biofilm-associated chronic respiratory infections due to P. aeruginosa, although it would be appropriate to conduct clinical studies to confirm this.
Community‐acquired pneumonia (CAP) in adults is an infectious disease with high morbidity in China and the rest of the world. With the changing pattern in the etiological profile of CAP and advances in medical techniques in diagnosis and treatment over time, Chinese Thoracic Society of Chinese Medical Association updated its CAP guideline in 2016 to address the standard management of CAP in Chinese adults. Extensive and comprehensive literature search was made to collect the data and evidence for experts to review and evaluate the level of evidence. Corresponding recommendations are provided appropriately based on the level of evidence. This updated guideline covers comprehensive topics on CAP, including aetiology, antimicrobial resistance profile, diagnosis, empirical and targeted treatments, adjunctive and supportive therapies, as well as prophylaxis. The recommendations may help clinicians manage CAP patients more effectively and efficiently. CAP in pediatric patients and immunocompromised adults is beyond the scope of this guideline. This guideline is only applicable for the immunocompetent CAP patients aged 18 years and older. The recommendations on selection of antimicrobial agents and the dosing regimens are not mandatory. The clinicians are recommended to prescribe and adjust antimicrobial therapies primarily based on their local etiological profile and results of susceptibility testing, with reference to this guideline.
These findings suggest that lung fibrotic changes caused by SARS disease occurred mostly in severely sick patients and may be self-rehabilitated. D(LCO) scores might be more sensitive than HRCT when evaluating lung fibrotic changes.
The aim of this study was to compare the efficacy and safety of tigecycline, a newly developed glycylcycline antibiotic, with those of empirical antibiotic regimens which have been reported to possess good efficacy for complicated skin and skin structure infections (cSSSIs), complicated intra-abdominal infections (cIAIs), community-acquired pneumonia (CAP), and other infections caused by methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE CI ؍ 0.69 to 1.07, P ؍ 0.19). The incidence of adverse events in the tigecycline group was significantly higher than that in the other therapy groups with a statistical margin (for the modified intent-to-treat [mITT] population, OR ؍ 1.33, 95% CI ؍ 1.17 to 1.52, P < 0.0001), especially in the digestive system (mITT population, OR ؍ 2.41, 95% CI ؍ 1.67 to 3.46, P < 0.00001). No difference regarding all-cause mortality and drug-related mortality between tigecycline and the other regimens was found, although numerically higher mortality was found in the tigecycline group. This meta-analysis provides evidence that tigecycline monotherapy may be used as effectively as the comparison therapy for cSSSI, cIAIs, CAP, and infections caused by MRSA/VRE. However, because of the high risk of mortality, AEs, and emergence of resistant isolates, prudence with the clinical use of tigecycline monotherapy in infections is required.The threat of antimicrobial resistance has been identified as one of the major challenges facing public health, and antimicrobial resistance has increased rates of morbidity and mortality and socioeconomic costs. The rapid rate of microbial evolution underscores the urgent need for development of new agents that overcome existing mechanisms of resistance displayed by multidrug-resistant bacteria.Tigecycline is a first-in-class expanded-broad-spectrum glycylcycline. It inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit but with a five times higher affinity than that for the tetracyclines (4). In vitro studies demonstrate that it has good activity against many commonly encountered respiratory bacteria, including multiple resistant Gram-positive, Gram-negative, anaerobic, as well as multidrug-resistant (MDR) pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE), vancomycin-resistant Enterococcus (VRE), penicillin-resistant Streptococcus pneumoniae (PRSP), and -lactamase-producing Haemophilus influenzae, among others (5). Tigecycline overcomes the two key tetracycline resistance mechanisms (efflux pumps and ribosomal protection) and is unaffected by other bacterial mechanisms of resistance, such as extended-spectrum -lactamases (32).Tigecycline was first approved for use for indications of complicated skin and skin structure infections (cSSSIs) and complicated intra-abdominal infections (cIAIs). Currently, it is approved for use for community-acquired pneumonia (CAP). It has also been found to be effective for the trea...
Background Clinical practice guidelines or recommendations often require timely and regular updating as new evidence emerges, because this can alter the risk-benefit trade-off. The scientific process of developing and updating guidelines accompanied by adequate implementation can improve outcomes. To promote better management of patients receiving vancomycin therapy, we updated the guideline for the therapeutic drug monitoring (TDM) of vancomycin published in 2015. Methods Our updated recommendations complied with standards for developing trustworthy guidelines, including timeliness and rigor of the updating process, as well as the use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. We also followed the methodology handbook published by the National Institute for Health and Clinical Excellence and the Spanish National Health System. Results We partially updated the 2015 guideline. Apart from adults, the updated guideline also focuses on pediatric patients and neonates requiring intravenous vancomycin therapy. The guideline recommendations involve a broadened range of patients requiring TDM, modified index of TDM (both 24-hour area under the curve and trough concentration), addition regarding the necessity and timing of repeated TDM, and initial dose for specific subpopulations. Overall, 1 recommendation was deleted and 3 recommendations were modified. Eleven new recommendations were added, and no recommendation was made for 2 clinical questions. Conclusions We updated an evidence-based guideline regarding the TDM of vancomycin using a rigorous and multidisciplinary approach. The updated guideline provides more comprehensive recommendations to inform rational and optimized vancomycin use and is thus of greater applicability.
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