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Polymyxin B and polymyxin E (colistin) are presently considered the last line of defense against human infections caused by multidrug-resistant Gram-negative organisms such as carbapenemase-producer Enterobacterales, Acinetobacter baumannii, and Klebsiella pneumoniae. Yet resistance to this last-line drugs is a major public health threat and is rapidly increasing. Polymyxin S2 (S2) is a polymyxin B analogue previously synthesized in our institute with obviously high antibacterial activity and lower toxicity than polymyxin B and colistin. To predict the possible resistant mechanism of S2 for wide clinical application, we experimentally induced bacterial resistant mutants and studied the preliminary resistance mechanisms. Mut-S, a resistant mutant of K. pneumoniae ATCC BAA-2146 (Kpn2146) induced by S2, was analyzed by whole genome sequencing, transcriptomics, mass spectrometry and complementation experiment. Surprisingly, large-scale genomic inversion (LSGI) of approximately 1.1 Mbp in the chromosome caused by IS26 mediated intramolecular transposition was found in Mut-S, which led to mgrB truncation, lipid A modification and hence S2 resistance. The resistance can be complemented by plasmid carrying intact mgrB. The same mechanism was also found in polymyxin B and colistin induced drug-resistant mutants of Kpn2146 (Mut-B and Mut-E, respectively). This is the first report of polymyxin resistance caused by IS26 intramolecular transposition mediated mgrB truncation in chromosome in K. pneumoniae. The findings broaden our scope of knowledge for polymyxin resistance and enriched our understanding of how bacteria can manage to survive in the presence of antibiotics.
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Objective:To explore the clinical characteristics, chest imaging manifestations, RAPID score and therapeutic situation in patients with parapneumonic pleural effusion (PPE) caused by streptococcus anginosus group (SAG), in order to provide help for the early diagnosis and treatment in clinical practices. Methods:The clinical data of 39 patients with PPE caused by SAG from January 2015 to May 2020 in Affiliated Hospital of Jining Medical University and Jining First People′s Hospital were retrospectively analyzed. The patients were classified by RAPID score.Results:Among 39 cases, males was in 31 cases (79.5%), females in 8 cases (20.5%), and aged 46 to 89 (65.31±10.53) years old. Fever was in 27 cases (69.2%), chest pain in 19 cases (48.7%), and dyspnea in 18 cases (46.2%). The chest CT findings showed consolidation shadows was in 30 cases (76.9%), encapsulated pleural effusion in 21 cases (53.8%), ground glass shadow in 18 cases (46.2%), nodules in 12 cases (30.8%), atelectasis in 8 cases (20.5%), and pneumothorax in 5 cases (12.8%). The complexity PPE was in 23 cases (59.0%), and empyema in 16 cases (41.0%). The microbiological culture results showed that streptococcus constellatus was detected in 25 cases (64.1%), streptococcus anginosus in 13 cases (33.3%), and streptococcus intermadius in 1 case (2.6%). After comprehensive treatment, 36 cases (92.3%) were improved, 3 cases (7.7%) died. According to the RAPID score, low-risk was in 13 cases (33.3%), intermediate-risk in 16 cases (41.0%), and high-risk in 10 cases (25.7%). The RAPID score in patients with low-risk, intermediate-risk and high-risk was (1.85 ± 0.38), (3.43 ± 0.51) and (5.30 ± 0.67) scores, and there was statistical difference ( F = 124.88, P<0.05). the length of stay in patients with low-risk, intermediate-risk and high-risk of RAPID score was (16.84 ± 5.57), (16.56 ± 7.05) and (28.20 ± 17.97) d, and there was statistical difference ( F = 4.41, P<0.05); the length of stay in patients with high-risk was significantly longer than that in patients with low-risk and intermediate-risk, and there was statistical difference ( P<0.05), there was no statistical difference between intermediate-risk patients and low-risk patients ( P>0.05). Conclusions:SAG, as important pathogens for the PPE, tends to induce CPPE and even pyopneumothorax. Clinical manifestations and imaging are not specific, which should be payed attention in clinical work. The patients with high-risk of RAPID score have more serious condition and worse prognosis.
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A total of 159 patients with Streptococcus milleri (S. milleri) infection were diagnosed in our hospital between January 2014 and January 2019. The demographic data, underlying diseases, infection sites, laboratory tests, and prognosis of patients were retrospectively analyzed; the clinical and microbiological data were compared among different age groups. Of the 159 patients there were 103 were males and 56 females; there were 19 patients aged<18 years [(8.1±5.3) years], 113 patients aged ≥18 and < 65 years [(45.5±13.1) years] and 27 patients aged ≥65 years[(74.7±8.6) years]. The incidence peaked in the 34-55 year age group (50 cases, 31.4%). Streptococcus anginosus was identified in 97 cases (61.0%), Streptococcus constellatus in 55 patients (34.6%) and Streptococcus intermedius in 7 cases (4.4%). The abdomen (44 cases, 27.7%) and the chest (19 cases, 11.9%) were the main involving sites. For patients younger than 18 years and those aged ≥18 and<65 years, suppurative appendicitis was the most common condition[12 cases(12/19) and 21 cases(18.6%), respectively]; while in patients aged ≥65 years, chest infection ranked the first (9 cases, 33.3%). All 159 patients were treated with anti-infection therapy alone or anti-infection and invasive procedures with a favorable prognosis, 2 patients died with a overall fatality rate of 1.3%.
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Bacteremia is a life-threating syndrome often caused by methicillin-resistant (MRSA). Thus, there is an urgent need to develop novel approaches to successfully treat this infection. Staphylococcal accessory regulator A (SarA), a global virulence regulator, plays a critical role in pathogenesis and -lactam antibiotic resistance in . Hypericin is believed to act as an antibiotic, antidepressant, antiviral and non-specific kinase inhibitor. In the current study, we investigated the impact of hypericin on -lactam antibiotics susceptibility and mechanism(s) of its activity. We demonstrated that hypericin significantly decreased the minimum inhibitory concentrations of -lactam antibiotics (.., oxacillin, cefazolin and nafcillin), biofilm formation and fibronectin binding in MRSA strain JE2. In addition, hypericin significantly reduced expression, and subsequently decreased and virulence-related regulators (.., ) and genes (.., and ) expression in the studied MRSA strain. Importantly, the synergistic effect of hypericin with -lactam antibiotic (.., oxacillin) translated into therapeutic outcome in a murine MRSA bacteremia model. These findings suggest that hypericin plays an important role in abrogation of -lactam resistance against MRSA through inhibition, and may allow us to repurpose the use of -lactam antibiotics, which are normally ineffective in the treatment of MRSA infections (.., oxacillin).
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Objective To analyze and review clinical characteristics of brucellosis and improve awareness of brucellosis and level of diagnosis.Methods Totally 72 in-patients treated for brucellosis from March 2012 to June 2015 in Affiliated Hospital of Jining Medical University were retrospectively analyzed for epidemiology,clinical feature,laboratory data,treatment and prognosis.Results A total of 72 cases were confirmed and included.Thirty seven patients (51.39％) had definitely contact history with raw meat or progeny and 3 (4.17％) with brucellosis patients.The common clinical presentations included persistent fever (100.00 ％,72/72),followed by headache (87.50％,63/72),chills (48.61％,35/72),muscle-joint pain (47.22％,34/72) and cough (43.06％,31/72).The laboratory test showed there were 14 patients (19.44％,14/72) with decreased leukopenia,49 patients (68.06％,49/72) with elevated C-reactive protein and 46 patients (63.89％,46/72) with elevated procalcitonin.Abnormal liver function showed elevated alanine aminotransferase (69.44％,50/72),aspartate aminotransferase (66.67％,48/72) and alkaline phosphatase (61.11％,44/72) with proportions.The mainly abnormal imaging features showed hepatomegaly,splenomegaly,lymphadenopathy,pulmonary infiltrating and nodules.Sixty-five patients (90.28％) had positive blood culture and 13 cases (18.06％) had positive marrow culture.Seventy-two patients were cured after active medical treatment and no recurrence after 1 year of follow-up.Conclusions Brucellosis is a invasive infectious disease with many systemic involvements,whose clinical symptoms are not typical.For those patients with long-term fever of unknown origin and poor effect anti-infection treatment,especially complicated with multi-system damage hepatomegaly,splenomegaly,lymphadenopathy,brucellosis should be suspected and be treated early.
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Objective@#To evaluate the efficiency of clear aligners in treating bimaxillary protrusion patients with first premolar extractions.@*Methods@#Eleven patients with bimaxillary protrusion were selected in this study. All of them were treated by using clear aligners with four first premolar extractions and need maximal anchorage. Cephalometric analysis was carried out before and after treatment.@*Results@#Cephalometric analysis results showed that significant changes in teeth and profile could be detected after clear aligner treatment and no change could be found in skeletal pattern. Upper and lower anterior teeth were retracted. The control of anterior torque and posterior anchorage were effective. The soft tissue analysis showed that position of upper and lower lip was significantly changed which improve the profile of patients. After treatment, the distance of U1 to NA and L1 to NB reduced by (5.19±4.12) mm and (4.53±1.20) mm, respectively. The differences were statistically significant (P<0.01).@*Conclusions@#Bimaxillary protrusion patients who needed premolar extractions and maximal anchorage could be treated with clear aligners.
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Inosine 5'-monophosphate dehydrogenase (IMPDH) is a key enzyme of de novo GMP biosynthesis. The expression and activity of IMPDH can be affected by diseases and physiological process. It is the drug target for anticancer, antiviral, antimicrobial and immunosuppressive therapeutics. Not only catalytic action but the other biological functions of IMPDH also play an important role in diseases. The basic functions, mechanism of catalysis, classification of inhibitors, biological functions and the latest advances to IMPDH will be illustrated in this review. It is expected to be helpful to the discovery of new inhibitors and biological functions of IMPDH.