Fabrication of levofloxacin-loaded porcine acellular dermal matrix hydrogel and functional assessment in urinary tract infection.

Bacterial cystitis, a commonly occurring urinary tract infection (UTI), is renowned for its extensive prevalence and tendency to recur. Despite the extensive utilization of levofloxacin as a conventional therapeutic approach for bacterial cystitis, its effectiveness is impeded by adverse toxic effects, drug resistance concerns, and its influence on the gut microbiota. This study introduces Lev@PADM, a hydrogel with antibacterial properties that demonstrates efficacy in the treatment of bacterial cystitis. Lev@PADM is produced by combining levofloxacin with decellularized porcine acellular dermal matrix hydrogel and exhibits remarkable biocompatibility. Lev@PADM demonstrates excellent stability as a hydrogel at body temperature, enabling direct administration to the site of infection through intravesical injection. This localized delivery route circumvents the systemic circulation of levofloxacin, resulting in a swift and substantial elevation of the antimicrobial agent's concentration specifically at the site of infection. The in vivo experimental findings provide evidence that Lev@PADM effectively prolongs the duration of levofloxacin's action, impedes the retention and invasion of E.coli in the urinary tract, diminishes the infiltration of innate immune cells into infected tissues, and simultaneously preserves the composition of the intestinal microbiota. These results indicate that, in comparison to the exclusive administration of levofloxacin, Lev@PADM offers notable benefits in terms of preserving the integrity of the bladder epithelial barrier and suppressing the recurrence of urinary tract infections.

Metagenomic next-generation sequencing of plasma cell-free DNA improves the early diagnosis of suspected infections.

BACKGROUND: Metagenomic next-generation sequencing (mNGS) could improve the diagnosed efficiency of pathogens in bloodstream infections or sepsis. Little is known about the clinical impact of mNGS test when used for the early diagnosis of suspected infections. Herein, our main objective was to assess the clinical efficacy of utilizing blood samples to perform mNGS for early diagnosis of suspected infections, as well as to evaluate its potential in guiding antimicrobial therapy decisions. METHODS: In this study, 212 adult hospitalized patients who underwent blood mNGS test in the early stage of suspected infections were enrolled. Diagnostic efficacy of mNGS test and blood culture was compared, and the clinical impact of mNGS on clinical care was analyzed. RESULTS: In our study, the total detection rate of blood mNGS was significantly higher than that of culture method (74.4% vs. 12.1%, P < 0.001) in the paired mNGS test and blood culture. Blood stream infection (107, 67.3%) comprised the largest component of all the diseases in our patients, and the detection rate of single blood sample subgroup was similar with that of multiple type of samples subgroup. Among the 187 patients complained with fever, there was no difference in the diagnostic efficacy of mNGS when blood specimens or additional other specimens were used in cases presenting only with fever. While, when patients had other symptoms except fever, the performance of mNGS was superior in cases with specimens of suspected infected sites and blood collected at the same time. Guided by mNGS results, therapeutic regimens for 70.3% cases (149/212) were changed, and the average hospitalized days were significantly shortened in cases with the earlier sampling time of admission. CONCLUSION: In this study, we emphasized the importance of blood mNGS in early infectious patients with mild and non-specific symptoms. Blood mNGS can be used as a supplement to conventional laboratory examination, and should be performed as soon as possible to guide clinicians to perform appropriate anti-infection treatment timely and effectively. Additionally, combining the contemporaneous samples from suspected infection sites could improve disease diagnosis and prognoses. Further research needs to be better validated in large-scale clinical trials to optimize diagnostic protocol, and the cost-utility analysis should be performed.

Molecular tracking of carbapenem-resistant Acinetobacter baumannii clinical isolates: a multicentre study over a 4-year period across eastern China.

Introduction. Colonization by carbapenem-resistant Acinetobacter baumannii (CRAB) causes therapeutic and economic problems for critically ill patients.Gap Statement. The analysis of CRAB in China was limited to certain regions.Aims. To investigate the antibiotic susceptibility, molecular characterization and clonal relationship among CRAB isolates from multiple hospitals of eastern China.Methodology. Isolates from 29 tertiary hospitals from September 2015 to September 2018 were recovered. All strains were analysed using antimicrobial susceptibility testing to detect their tolerance. PCR was also used to detect multiple ß-lactamase genes. After multilocus sequence typing (MLST) of seven house-keeping genes. eBURST was used to assess clonal complexes and explore evolutionary relationships.Results. All isolates showed resistance to carbapenems, while remaining susceptible to colistin and tigecycline. All isolates were detected with bla OXA-51 gene by PCR, and 80.1 % harboured the bla OXA-23 gene. The prevalence of blaOXA-23 gene was remarkably increased from 50.7 % in 2015 to 90.5 % in 2018. Other genes such as bla OXA-24, bla OXA-58, bla IMP-2/4, bla VIM-2, bla SHV, bla AmpC and bla TEM were also obtained. While bla KPC, bla NDM-1, bla IMP-4 and bla SIM-1 were not found in these strains. MLST showed all isolates could be divided into 26 known sequence types (STs) and ten novel STs and 47.2 % isolates belong to ST195 and ST208. eBURST revealed clonal complex 92 as the major clonal complex (98.4 %), which includes 88.5 % (23/26) of known STs and 80 % (8/10) of unknown STs. Phylogenetic analysis also found that almost all CRAB isolates could cluster into one lineage, suggesting an epidemic of this CRAB lineage. This indicated severe nosocomial infections of CRAB in multiple hospitals of eastern China.Conclusion. An outbreak of ST195 and ST208 CRAB-resistant clones with bla OXA-23 gene might be happening in multiple hospitals in eastern China.

Malignant melanoma mimic fungal infection a case report.

BACKGROUND: Most of malignant melanomas originate from skin and often metastasize to the lungs, rarely metastasizes to the liver and bone. However, imageology characters of lung metastasis tumor are commonly similar to those of fungal infections. CASE PRESENTATION: A patient was admitted with unhealed plantar puncture wound for 3 years, and cough and expectoration for 2 years. The chest computed tomography (CT) revealed multiple nodules with cavities, and the patient was diagnosed of pulmonary fungal infection in another hospital and received antifungal therapy for more than 8 months, but the clinical symptoms and chest imaging findings continue to progress. After admission, the pathological results of both lung biopsy and biopsy of the plantar wound 3 years ago indicated malignant melanoma. CONCLUSIONS: The diagnosis of lung lesions cannot rely solely on imaging diagnosis, lung biopsy should be performed if necessary.

In vitro and in vivo Activity of Combinations of Polymyxin B with Other Antimicrobials Against Carbapenem-Resistant Acinetobacter baumannii.

PURPOSE: To study the in vitro and in vivo antibacterial activities of polymyxin B (PB) and other five antimicrobial agents, including imipenem (IMP), meropenem (MEM), tigecycline (TGC), sulbactam (SUL), and rifampicin (RIF), alone or in combination against carbapenem-resistant Acinetobacter baumannii (CRAB). METHODS: Microbroth dilution method was used to determine the minimum inhibitory concentration (MIC) of ten strains of CRAB against six antibacterial drugs, and the checkerboard method was used to determine the fractional inhibitory concentration index (FICI). A mouse pneumonia model was established by intranasal instillation of Ab5075 to evaluate the antibacterial activity in vivo. RESULTS: The resistance rate of ten CRAB strains to IMP, MEM, and SUL was 100%, that to PB and TGC was 0%, and that to RIF was 20%. When PB was used in combination with the other five antibiotics in vitro, it mainly showed synergistic and additive effects on CRAB. The synergistic effect of PB and RIF was maximal, followed by MEM and IMP but was weak with SUL and TGC. In vivo, compared to the model group (untreated with antibiotics), treatment group (six antibiotics alone and PB combined with the other five antibiotics) reduced the bacterial load in the lung tissue and the serum inflammatory factors (IL-1ß, IL-6, and TNF-α). The bacterial load and the inflammatory factors of the combined group decreased significantly than that of the single group (P<0.05). The IL-6 and TNF-α values of the PB combined with the RIF group were significantly lower than the two drugs used individually. CONCLUSION: The combination of PB and IMP, MEM, and RIF exerted robust in vitro synergistic effects on CRAB isolates. The combination of PB and the other five antimicrobial agents had a better effect in the mouse pneumonia model than single agent, while the combination of PB and RIF had the best effect.