ABSTRACT
The polymyxins are important antimicrobial agents against antibiotic-resistant gram-negative bacilli. In 2020, the Clinical and Laboratory Standards Institute modified the clinical breakpoints for polymyxin susceptibility test by eliminating the "susceptible" interpretive category, only reporting intermediate (≤2 mg/L) and resistant (≥4 mg/L). However, the European Committee on Antimicrobial Susceptibility Testing recommended the use of clinical breakpoints of ≤2 mg/L as susceptible and >2 mg/L as resistant. The first-line laboratorians and clinicians in China have been perplexed by the inconsistence of international polymyxin clinical breakpoints and discouraged by the difficulty of conducting polymyxin susceptibility testing. Therefore, it is urgently needed to make it clear for the laboratorians in China to know how to accurately carry out polymyxin susceptibility testing and standardize the interpretation of susceptibility testing results. To this end, the experts from relevant fields were convened to formulate this consensus statement on the testing and clinical interpretation of polymyxin susceptibility. Relevant recommendations are proposed accordingly for laboratorians and clinicians to streamline their daily work.
ABSTRACT
<p><b>BACKGROUND</b>Bacteria-induced respiratory infection has been long considered to be the major cause of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Therefore, a clear picture about the distribution and drug-resistance of pathogenic bacteria in the lower airways should be helpful for treatment of the disease. So far, data on this topic among Chinese are lacking.</p><p><b>METHODS</b>A surveillance study was performed in consecutive patients with AECOPD at five areas in China between October 2006 and April 2008. The sputum from these patients was cultured and isolated for bacteria. Agar dilution method was used to determine the minimal inhibitory concentrations (MICs) of levofoxacin and other 15 antibiotics against these strains.</p><p><b>RESULTS</b>Three hundred and fifty-nine pathogenic bacterial strains were isolated among 884 patients with AECOPD. The predominant bacteria were Pseudomonas aeruginosa (21.7%), Klebsiella pneumoniae (12.3%), Haemophilus influenzae (14.2%) and Streptococcus pneumoniae (11.7%), followed by Haemophilus parainfluenzae (9.5%), Acinetobacter baumannii (7.8%), Moraxella catarrhalis (6.4%) and Escherichia coli (3.6%). The majority of bacterial pathogens isolated in this study were susceptible to fuoroquinolones, ceftazidime, cefepime and imipenem.</p><p><b>CONCLUSIONS</b>Gram-negative bacilli are the leading pathogens in patients with AECOPD in China. Haemophilus parainfluenzae may be one of the most important pathogens in AECOPD. This study provides evidence for local surveillance of AECOPD pathogens and appropriate choice of antimicrobials in China.</p>
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Acute Disease , Bacteria , Drug Resistance, Bacterial , Microbial Sensitivity Tests , Pulmonary Disease, Chronic Obstructive , MicrobiologyABSTRACT
<p><b>BACKGROUND</b>It is the first multicenter clinical study in China to investigate zanamivir use among Chinese adolescents and adults with influenza-like illness (ILI) since 2009, when inhaled zanamivir (RELENZA(®)) was marketed in China.</p><p><b>METHODS</b>An uncontrolled open-label, multicentre study to evaluate the antiviral activity, and safety of inhaled zanamivir (as Rotadisk via Diskhaler device); 10 mg administered twice daily for 5 days in subjects ≥ 12 years old with ILI. Patients were enrolled within 48 hours of onset and followed for eight days. Patients were defined as being influenza-positive if the real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) test had positive results.</p><p><b>RESULTS</b>A total of 400 patients ≥ 12 years old were screened from 11 centers in seven provinces from March 2010 to January 2011. Three hundred and ninety-two patients who took at least one dose of zanamivir were entered into the safety analysis. The mean age was 33.8 years and 50% were male. Cardiovascular diseases and diabetes were the most common comorbidities. All the reported adverse events, such as rash, nasal ache, muscle ache, nausea, diarrhea, headache, occurred in less than 1% of subjects. Mild sinus bradycadia or arrhythmia occurred in four subjects (1%). Most of the adverse events were mild and did not require any change of treatment. No severe adverse events (SAE) or fatal cases were reported. Bronchospasm was found in a 38 years old woman whose symptoms disappeared after stopping zanamivir and without additional treatment. All the 61 influenza virus isolates (43 before enrollment, 18 during treatment) proved to be sensitive to zanamivir.</p><p><b>CONCLUSIONS</b>Zanamivir is well tolerated by Chinese adolescents and adults with ILIs. There is no evidence for the emergence of drug-resistant isolates during treatment with zanamivir.</p>
Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Antiviral Agents , Therapeutic Uses , Influenza, Human , Drug Therapy , Treatment Outcome , Zanamivir , Therapeutic UsesABSTRACT
Objective To conduct an in vitro study of the growth of Pseudomonas aeruginosa,Staphylococcus aureus and Acin- etobacter spp.,and evaluate their response to various concentrations of tumor necrosis factor(TNF)-?,interleukin (IL)-1?, and IL-6.Methods To monitor the growth of bacteria incubated with the cytokines TNF?,IL-1?and IL-6 that were added to RPMI 1640 medium in various concentrations (10,50.100,500 pg,1 and 10 ng) at 2,4 to 6,8 and 16-18 h.The bacterial concentration was estimated when the mixtures of cytokines and specific neutralizing monoclonal antibodies (MoAbs) were in- cubated.Results We found that all three bacterial species showed concentration-dependent growth enhancement when incubated with one or more tested cytokines.Blockade by specific neutralizing cytokine significantly inhibited cytokine-induced growth. When compared with control,the 6 h growth response was maximal with IL-1?for Staphylococcus aureus and Acinetobacter spp.,and with IL-6 for Pseudomonas aeruginosa.Conclusions In this study we provide additional evidence for a newly de- scribed mechanism for bacterial proliferation in the presence of exaggerated and protracted inflammation.The effect that cyto kine-induced growth enhancement inhibited by specific neutralizing cytokine MoAbs may be useful for antimicrobial therapy.
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<p><b>OBJECTIVE</b>To investigate whether the effect of E. coli on U937 cell lines apoptosis is mediated via p38 mitogen-activated protein kinase (MAPK) activation.</p><p><b>METHODS</b>The U937 cell lines were treated with E. coli at different time or together with SB203580, an inhibitor for p38. Cell apoptosis was analyzed by flow cytometry. p38 activities were detected by Western blotting.</p><p><b>RESULTS</b>E. coli induced apoptosis in cultured U937 cell lines in a time-dependent manner. The phosphorylation of p38 was induced after 10 minutes infection, reached the peak after 20 minutes, and started to decline after 30 minutes. In contrast, the level of total p38 protein was not changed in whole experimental period. Inhibition of p38 with SB203580 significantly inhibited E. coli induced apoptosis in U937 cells.</p><p><b>CONCLUSION</b>The activation of the p38 MAPK in U937 cell lines by E. coli is a major pathway to mediate the apoptosis.</p>