Arthritis caused by Cryptococcus neoformans infection: A case report.

Cryptococcal infections are uncommon in individuals with normal immune functions. These infections commonly affect the lungs and central nervous system; however, there are a few reports of infection in the bone and joint areas. The current study reported a case of knee joint infection caused by Cryptococcus neoformans in China. A 56-year-old man presented to The China Academy of Chinese Medical Sciences Guang'anmen Hospital Baoding Hospital (Baoding, China) with severe anemia and lung inflammation. Initially, there was no obvious cause of swelling or pain in the knee joints. However, after the patient presented with new swollen and painful knee joint symptoms, pus culture and cryptococcal antigen detection tests confirmed C. neoformans infection. After pus drainage and fluconazole treatment, the patient's condition substantially improved. Clinical awareness of C. neoformans infections should be promoted. In suspected cases, puncture fluid or tissue pathogen testing should be performed as early as possible to avoid misdiagnosis and serious consequences of delayed treatment.

Listeriosis Cases and Genetic Diversity of Their L. monocytogenes Isolates in China, 2008-2019.

Listeriosis, caused by Listeria monocytogenes, is a severe food-borne infection. The nationwide surveillance in China concerning listeriosis is urgently needed. In the present study, 144 L. monocytogenes isolates were collected from the samples of blood, cerebrospinal fluid (CSF), and fetal membrane/placenta in China for 12 years from 2008 to 2019. We summarized these listeriosis patients' demographical and clinical features and outcomes. The susceptibility profile for 12 antibiotics was also determined by the broth microdilution method. Multilocus sequence typing (MLST) and serogroups of these listeria isolates were analyzed to designate epidemiological types. We enrolled 144 cases from 29 healthcare centers, including 96 maternal-neonatal infections, 33 cases of bacteremia, 13 cases of neurolisteriosis, and two cutaneous listeriosis. There were 31 (59.6%) fetal loss in 52 pregnant women and four (9.8%) neonatal death in 41 newborns. Among the 48 nonmaternal-neonatal cases, 12.5% (6/48) died, 41.7% (20/48) were female, and 64.6% (31/48) occurred in those with significant comorbidities. By MLST, the strains were distinguished into 23 individual sequence types (STs). The most prevalent ST was ST87 (49 isolates, 34.0%), followed by ST1 (18, 12.5%), ST8 (10, 6.9%), ST619 (9, 6.3%), ST7 (7, 4.9%) and ST3 (7, 4.9%). Furthermore, all L. monocytogenes isolates were uniformly susceptible to penicillin, ampicillin, and meropenem. In summary, our study highlights a high genotypic diversity of L. monocytogenes strains causing clinical listeriosis in China. Furthermore, a high prevalence of ST87 and ST1 in the listeriosis should be noted.

The role of the globular heads of the C1q receptor in TcdA-induced human colonic epithelial cell apoptosis via a mitochondria-dependent pathway.

BACKGROUND: Clostridioides (formerly Clostridium) difficile infection is the leading cause of antibiotic-associated colitis. Studies have demonstrated that C. difficile toxin A (TcdA) can cause apoptosis of many human cell types. The purpose of this study was to investigate the relationships among exposure to TcdA, the role of the receptor for the globular heads of C1q (gC1qR) gene and the underlying intracellular apoptotic mechanism in human colonic epithelial cells (NCM 460). In this study, gC1qR expression was examined using real-time polymerase chain reaction (PCR), western blotting and immunohistochemical staining. Cell viability was assessed by the water-soluble tetrazolium salt (WST-1) assay, and cell apoptosis was assessed by flow cytometry and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. Mitochondrial function was assessed based on reactive oxygen species (ROS) generation, changes in the mitochondrial membrane potential (ΔΨm) and the content of ATP. RESULTS: Our study demonstrated that increasing the concentration of TcdA from 10 ng/ml to 20 ng/ml inhibited cell viability and induced cell apoptosis (p < 0.01). Moreover, the TcdA-induced gC1qR expression and enhanced expression of gC1qR caused mitochondrial dysfunction (including production of ROS and decreases in the ΔΨm and the content of ATP) and cell apoptosis. However, silencing of the gC1qR gene reversed TcdA-induced cell apoptosis and mitochondrial dysfunction. CONCLUSION: These data support a mechanism by which gC1qR plays a crucial role in TcdA-induced apoptosis of human colonic epithelial cells in a mitochondria-dependent manner.

Multidrug-resistant Acinetobacter baumannii strains with NDM-1: Molecular characterization and in vitro efficacy of meropenem-based combinations.

Acinetobacter baumannii is an important cause of hospital-acquired, multidrug-resistant (MDR) infections occurring worldwide. Anti-microbial combination regimens may be the only feasible treatment option for affected patients. In the present study, the efficacy of the combined therapy of meropenem with colistin, ampicillin-sulbactam, tazobactam and vancomycin against clinical strains of MDR A. baumannii was determined. Anti-microbial susceptibility testing was performed and resistance genes were characterized by a multiplex polymerase chain reaction (PCR)-reverse line blot assay. The genetic background of New Delhi metallo-ß-lactamase 1 (NDM-1) was analysed by primer walking. The presence of NDM-1 was detected using the modified Hodge test and the EDTA-combined disk test. To screen for synergistic drug effects, the fractional inhibitory concentration index was calculated using a checkerboard assay. The results of the PCR as well as the sequence analyses suggested that NDM-1 was located downstream of the ISAba125 element. In addition, a synergistic effect was determined for meropenem + vancomycin, meropenem + tazobactam and meropenem + ampicillin + sulbactam in two strains each, and in four strains for meropenem + colistin. A total of five A. baumannii strains with resistance to numerous antibiotics and carrying numerous resistance genes were identified. In the strains of A. baumannii, the NDM-1 gene was integrated in a transposon structure with a copy of the ISAba125 insertion sequence. However, the genetic background was not identical among the different species and strains. The genetic variability of NDM-1 may facilitate the rapid dissemination of this gene. In conclusion, meropenem may enhance the efficacy of antibiotics in A. baumannii strains with NDM-1-associated MDR.

Role of vancomycin in the treatment of bacteraemia and meningitis caused by Elizabethkingia meningoseptica.

Elizabethkingia meningoseptica, a Gram-negative pathogen once deemed clinically insignificant, tends to cause infections among low-birth-weight infants and immunocompromised patients. Previously, vancomycin was reported to cure several patients with bacteraemia caused by E. meningoseptica. Nevertheless, some laboratory investigations also showed considerable discordance between in vitro vancomycin susceptibility results obtained by the disk diffusion and broth microdilution methods against clinical E. meningoseptica isolates as determined using the criteria for staphylococci recommended by the Clinical and Laboratory Standards Institute (CLSI). In this review, the PubMed database (1960-2017) was searched for studies that reported mainly cases with E. meningoseptica bacteraemia or meningitis treated with vancomycin alone or with regimens that included vancomycin. In addition, the in vitro synergy between vancomycin and other agents against isolates of E. meningoseptica was reviewed. Elizabethkingia meningoseptica bacteraemia appears not to universally respond to intravenous (i.v.) vancomycin-only therapy, especially in patients who require haemodialysis. If i.v. vancomycin is the favoured therapy against E. meningoseptica meningitis, the addition of ciprofloxacin, linezolid or rifampicin might be an option to effectively treat this difficult-to-treat infection. Further clinical studies are needed to determine the clinical efficacy of these combination regimens for the treatment of E. meningoseptica meningitis.

Molecular characterization of resistance, virulence and clonality in vancomycin-resistant Enterococcus faecium and Enterococcus faecalis: A hospital-based study in Beijing, China.

The incidence of vancomycin-resistant enterococcus (VRE) in China is increasing, the molecular epidemiology of VRE in China is only partly known. This study was conducted to assess the molecular characterization of resistance, virulence and clonality of 69 vancomycin-resistant Enterococcus faecium (VREfm) and seven vancomycin-resistant Enterococcus faecalis (VREfs) isolates obtained from a Chinese hospital between July 2011 and July 2013. The glycopeptide resistance genes (VanA and VanB) were screened by multiplex PCR. The presence of five putative virulence genes (esp, gelE, asa1, hyl and cylA) were evaluated by another multiplex PCR. Multilocus sequence typing (MLST) scheme was used to assess the clonality. All 76 VRE isolates exhibited VanA phenotype and harbored VanA gene. Esp was the only gene detected both in VREfm and VREfs strains, accounting for 89.9% and 42.9%, respectively. The hyl gene was merely positive in 27.5% of VREfm strains. MLST analysis demonstrated three STs (ST6, ST4 and ST470) in VREfs and twelve STs (ST78, ST571, ST17, ST564, ST389, ST18, ST547, ST341, ST414, ST343, ST262 and ST203) in VREfm, which were all designated as CC17 by eBURST algorithm. An outbreak of VREfm belonging to ST571 was found to happen within the neurology ward in this hospital. To our knowledge, this is the first report of ST6 (CC2) VREfs strains in China and the first outbreak report of VREfm strains belonging to ST571 around the world. Our data could offer important information for understanding the molecular features of VRE in China.

[Establishment of early warning control charts based on the syndromic surveillance data of outpatient diarrhea in Beijing].

OBJECTIVE: To establish the control charts for early warning of diarrhea based on the syndromic surveillance data from enteric clinic in Beijing. METHODS: The outpatient data from enteric clinic of a Grade Three General hospital in Haidian district, Beijing from April 1 to Oct. 31, 2009 and from May 1 to Nov.10, 2010 were collected, according to the moving average method, the baseline calculated, the value of probability α and µα, the early warning value based on the formula "w=Xj+µαSj" calculated and the early warning control charts drew at last. RESULTS: According to the harmfulness, the severity and controllability of diarrheal diseases, the value of probability α was determined as 0.01, then µα (unilateral) as 2, based on the early warning value, the control charts of diarrheal diseases, bacillary dysentery and other infectious diarrhea were established. CONCLUSION: The enteric clinic requires to further collect baseline data to evaluate and continuously adjust the established control charts for the best early warning model in accordance with the enteric clinic.

[The change and significance of vancomycin minimal inhibitory concentration against methicillin-resistant Staphylococcus aureus isolates from inpatients with lower respiratory tract infection].

OBJECTIVE: To investigate the change and significance of vancomycin minimal inhibitory concentration (MIC) against methicillin-resistant Staphylococcus aureus (MRSA) isolates. METHODS: We analyzed the data of inpatients with lower respiratory tract infection, with positive cultures of MRSA from airway samples, at respiratory ward or respiratory intensive care unit (RICU) between 2000 and 2011. The MIC of vancomycin was determined by the agar dilution method. RESULTS: There were 295 patients [210 males, 85 females, mean age (73 ± 12) years (range, 18 - 98)] with a positive culture of MRSA from airway samples. The arithmetic mean of vancomycin MIC against MRSA isolates fluctuated from 0.99 to 1.60 mg/L. The number of defined daily doses (DDDs) of vancomycin from the whole hospital had an influence on the mean of vancomycin MIC in the next year (r = 0.64, P = 0.04). But the vancomycin DDDs from respiratory department were not related with the mean of vancomycin MIC in the next year (r = 0.33, P = 0.32). The patients were divided into 2 groups according the MIC of vancomycin against MRSA isolates: MIC = 2 mg/L group (n = 43) and MIC < 2 mg/L group (n = 252). There was no difference in mortality [14 cases (32.6%) and 73 cases (29.0%)] (χ(2) = 0.23, P = 0.63), the clinical success rates [26 cases (60.5%) and 156 cases (61.9%)](χ(2) = 0.03, P = 0.85) and bacterial success rates [21 cases (48.8%) and 106 cases (42.1%)] (χ(2) = 1.20, P = 0.27) between the 2 groups. But the average hospitalization days were significantly prolonged (Z = 3.09, P = 0.00)in the MIC = 2 mg/L group [40(27, 93) days]as compared to that in the MIC < 2 mg/L group [30 (20, 52) days]. The average treatment time [10 (1, 19) days and 3(0, 12) days, Z = -2.79, P < 0.01] was also longer in the MIC = 2 mg/L group. In a multiple stepwise regression analysis, male gender (OR = 3.58) and acute physiology and chronic health evaluation II (APACHE II) scores (OR = 1.06) were independently associated with vancomycin MIC = 2 mg/L. CONCLUSIONS: In inpatients with MRSA lower respiratory tract infection at respiratory ward or RICU between 2000 and 2011, the vancomycin MIC fluctuated, which was related with vancomycin DDDs from the whole hospital. The average hospitalization days and treatment time were significantly prolonged in patients with MRSA isolates with a higher vancomycin MIC (= 2 mg/L). APACHE II score was an independent risk factor for vancomycin MIC being 2 mg/L.

[Physiological changes in serum procalcitonin concentrations in premature infants early after birth].

OBJECTIVE: To investigate serum procalcitonin (PCT) concentrations in premature infants with different gestational ages at different times after birth. METHODS: A total of 217 neonates without infection, including 102 premature infants and 115 full-term infants, were enrolled in this study. The premature infants were further divided by gestational age into three subgroups: 30-32 weeks (n=30), 33-34 weeks (n=35) and 35-36 weeks (n=37). All the infants were studied to evaluate serum PCT concentrations at 0-12, 13-24, 25-36, 37-48, 49-72, 73-96, 97-120 and 121-144 hours after birth. RESULTS: In the newborns, serum PCT concentrations increased gradually after birth, reached peak values at about 24 hours after birth, and then gradually declined and dropped to normal values for children at about 96 hours after birth. In the premature infants, serum PCT concentrations reached peak values at about 36 hours after birth, later than in the full-term infants, then declined slowly and dropped to levels similar to the full-term infants at 96 hours after birth. Serum PCT concentrations in the 30-32 week subgroup remained at low levels after birth, and increased gradually, later than in other premature infants, at 37-48 hours after birth. CONCLUSIONS: Early after birth, neonates have a changing serum PCT concentration, increasing first and then decreasing. Peak serum PCT levels appear later in premature infants than in full-term infants. Serum PCT concentrations of premature infants with a gestational age of under 32 weeks remain at relatively low levels within 36 hours after birth.

Relationship between time to positivity of blood culture with clinical characteristics and hospital mortality in patients with Escherichia coli bacteremia.

BACKGROUND: Previous studies indicated that the time to positivity (TTP) of blood culture is a parameter correlating with degree of the bacteremia and outcome in patients with bloodstream infections caused by Escherichia coli (E. coli). The objective of this study was to further investigate the diagnostic and prognostic power of using TTP to predict E. coli bacteremia. METHODS: A retrospective cohort study at two university hospitals was conducted. We retrieved all the medical records of those with E. coli bloodstream infection according to the records generated by their microbiology departments. Univariate and multivariate analyses were applied to identify clinical factors correlating with fast bacterial growth and significant prognostic factors for hospital mortality. RESULTS: Medical records of 353 episodes of E. coli bacteremia diagnosed between January 1, 2007 and December 31, 2009 were retrieved in the investigation. Univariate analysis demonstrated that the TTP ≤ 7 hours group is associated with higher incidence of active malignancies (41.7% vs. 27.2%, P = 0.010), neutropenia (30% vs.14.3%, P = 0.007), primary bacteremia (55.0% vs. 33.4%, P = 0.002), and poorer outcome (hospital mortality 43.3% vs.11.9%, P = 0.000) than the TTP > 7 hours group. Multivariate analysis revealed that the significant predictors of hospital mortality, in rank order from high to low, were TTP (for TTP ≤ 7 hours, odds ratio (OR): 4.886; 95% confidence interval (CI): 2.572 - 9.283; P = 0.000), neutropenia (OR: 2.800; 95%CI: 1.428 - 5.490; P = 0.003), comedication of steroids or immunosuppressive agents (OR: 2.670; 95%CI: 0.971 - 7.342; P = 0.057). CONCLUSIONS: Incidence of malignancies, neutropenia and primary bacteremia correlates with fast bacterial growth in patients with E. coli bacteremia. The parameter of TTP has been identified as a variable of highest correlation to hospital mortality and therefore can be potentially utilized as a mortality prognostic marker.

[Correlation between in vitro bacterial growth velocity of blood of patients with clinical parameters and prognosis in patients with Escherichia coli bacteremia].

OBJECTIVE: To identify the clinical and laboratory parameters correlating with speed of bacterial growth in culture and independent risk factors of in-hospital mortality in patients with Escherichia coli bacteremia. METHODS: This retrospective study was conducted at Beijing University Third Hospital. The medical records and microbiological database of the patients diagnosed as Escherichia coli bacteremia between January 2007 and December 2009 were collected. The parameter of time to positivity (TTP) was used to be a surrogate marker of bacterial growth. Univariate analysis was used to identify relationship between clinical parameters and the speed of bacterial growth. Logistic multivariate analysis was used to identify risk factors of in-hospital mortality. RESULTS: The medical records of 112 patients during the study period were collected, 25 patients died during hospital stay, the overall in-hospital mortality rate was 22.3%. Univariate analysis indicated the rapid-growth (TTP≤7 hours) group (n=20) had higher incidence of neutropenia (40.0% vs. 15.2%), higher incidence of primary bacteremia (40.0% vs. 18.5%) and higher in-hospital mortality rate (45.0% vs. 17.4%) than those with slow bacterial growth (TTP>7 hours) group (n =92, all P<0.05). The death group (n=25) was found to have a higher incidence of TTP≤7 hours (36.0% vs. 12.6%), higher incidence of active malignancies (44.0% vs. 24.1%), higher incidence of neutropenia (36.0% vs. 14.9%), higher rate of isolation of extended spectrum ß lactamases (ESBL)-producing strains (48.0% vs. 24.1%) than the survival group (n=87, all P<0.05). Logistic multivariate analysis suggested the significant predictors of in-hospital mortality included TTP≤7 hours [odds ratio (OR)=3.412, 95% confidence interval (95% CI)=1.1819.856, P=0.023], ESBL-producing strains (OR=2.545, 95% CI=0.9776.625, P=0.056). CONCLUSION: In vitro Escherichia coli growth speed in the blood culture correlates with the incidence of neutropenia and primary bacteremia, and TTP≤7 hours and ESBL-producing strains may be the strong, independent risk factors of a worse prognosis in patients with Escherichia coli bacteremia.

[Analysis of disease types of outpatients with intestinal diseases from two grade-three general hospitals in Beijing].

OBJECTIVE: To understand the spectrum of diseases and epidemiological characteristics of outpatients at Entric Disease Clinic, with a focus on analysis of the distribution of infectious diarrheal diseases in different populations and to explore disease control strategies on Enteric Infectious Diseases for focal groups. METHODS: A census on outpatients at Entric Disease Clinics was conducted in two class Three comprehensive hospitals in Beijing from April 1 to October 31, 2009 based on a descriptive study using diarrhea-syndrome surveillance system set in the two clinics, thus to depict the spectrum of diseases and epidemiological characteristics of outpatients, and analyze the proportion of infectious diarrhea in diarrheal diseases specifically and the rate changes of infectious diarrhea in different months, age groups and occupational groups. RESULTS: Diseases are varied at the two enteric diseases clinics among the patients and there are mainly 10 kinds of diseases, "non-infectious diarrhea" accounted for the highest percentage (77.4%), followed by "unspecified diarrhea" (11.7%), and infectious diarrhea accounted for the least proportion(8.7%)."Gastroenteritis and enteritis" are the most frequently diagnosed cases among all the diseases, was a total of 7 565 cases, accounting for 70.2%. The volume of visits reached its top during summer and autumn(July to September), and the mean volume of visits in this period is (60.78+/-16.85) cases/day. The volume of visits has an obvious seasonal trend, and visits during July and August are the most frequent (41.82% altogether). Patients with "infectious diarrhea" had a highest ratio(5.3%) in May and lowest (1.1%) in October while patients with "bacillary dysentery" accounted for a highest ratio(8.2%) in September and lowest(3.8%) in April. Outpatients are mainly from Beijing city(61.9%), in which young and middle-aged people accounted for 73.9% in total, and student is the main occupation (28.8%). The distributions of diarrheal diseases are the same in different age groups but differ from different occupational groups. Infectious diarrhea accounted for a highest proportion(9.2%) in 18-to-44-year-old age group when using age grouping, and a highest proportion(15.2%) in restaurant service personnel when using occupation grouping. CONCLUSION: The volume of outpatients attended at general hospitals is overwhelming especially in July and August, and the major type is "non-infectious diseases", which indicates an arduous task on prevention and control of Enteric Infectious Diseases. Infectious diarrhea took up a certain amount, but the rate is not that high, which indicates possible missing diagnosis of patients with infectious diseases.Our focal groups would be young and middle-aged people and students in the city. Therefore, the need to extend the consultation hours is urgent. Meanwhile, for the main goal of surveillance and early warning on Enteric Infectious Diseases, all aspects of construction of Enteric Disease Clinic should be strengthened, such as enhance laboratory tests on pathogens, improve diagnosis level of physicians and etc.

[Molecular mechanism of multiple-drug and pan-drug resistance among Acinetobacter species].

OBJECTIVE: To investigate the molecular mechanism of multiple-drug and pan-drug resistance among Acinetobacter species. METHODS: Non-repetitive 90 carbapenem-resistant strains of Acinetobacter species were collected in Beijing, Guangzhou, and Fuzhou 1999-2004. The homology of the isolates was determined by both pulsed field gel electrophoresis and randomly amplified polymorphic DNA typing. Seven representative clones were selected from the 90 strains of Acinetobacter isolated from different hospitals to be used for further study. Analytical isoelectric focusing was used to measure the isoelectric point of the beta-lactamase. Plasmid DNA was extracted and purified Genes of different beta-lactamase, including bla(TEM--), bla(SHV-), bla(PER-), blaI(MP-), bla(VIM-), and bla(OXA-) genes, in these clone strains were amplified and sequenced. PCR was used to analyze the integrons. RESULTS: The P clone strain isolated during an outbreak of pan-drug-resistant Acinetobacter species in Peking Union Medical College Hospital 2004 was not susceptible to most common antimicrobial agents tested. The 7 representative clones produced multiple beta-lactamases: TEM-1, high-level AmpC, SHV-type, OXA-23 carbapenemase and IMP-8 and metalloenzyme respectively. One clone produced PER-1 enzyme. These 7 clone strains were resistant to most beta-lactams (including carbapenems), erythromycin, chloramphenicol, and rifampin. Two clone strains were susceptible to cefoperazone/sulbactam and amikacin while 4 clone strains susceptible to levofloxacin. All of the 7 clones were susceptible to minocycline and colistin. Five different integrons were found, harboring the genes mediating the resistance to aminoglycosides, rifampin, chloramphenicol, and carbapenems (bla(IMP-8)). CONCLUSION: The molecular bases of multiple-drug or pan-drug resistance in Acinetobacter species include production of OXA-23 carbapenemase or IMP type metalloenzyme and integrons with different resistance gene cassettes. Pan-drug-resistant Acinetobacter species are susceptible to old antimicrobials agents, such as colistin and minocycline.