Clinical outcome of invasive infections in children caused by highly penicillin-resistant Streptococcus pneumoniae compared with infections caused by penicillin-susceptible strains

BACKGROUND: In this report based on data from the Institutional Surveillance System during 1994-1998, we document the continuing emergence of drug-resistant Streptococcus pneumoniae strains at the Hospital Infantil de Mexico Federico Gómez in Mexico City. METHODS: We evaluate the clinical course of 49 invasive pneumococcal infection outside the central nervous system (CNS) by a number of factors including the site, severity, and place where the infection was acquired, the underlying health of the patient, and the adequacy of antimicrobial therapy. RESULTS: An underlying illness was present in 21 of 49 (43%) patients, 37 (75%) patients had taken previous antimicrobial therapy, and 25% of the infections were nosocomially acquired. Overall, 25 of 49 (51%) of the pneumococcal strains tested were pencillin-resistant; strains with the highest resistance to penicillin were also resistant to cephalosporins. Twenty-two percent of all strains were considered to be multidrug-resistant. Eleven of 25 penicillin-resistant strains were identified as multidrug-resistant, i.e., to erythromycin, TMP/SMX, and chloramphenicol. Ten serotypes accounted for 88% of the isolates, the most frequent serotypes being 23F, 14, 19V, 6A, and 6B. The overall case-fatality rate was 37% (18 of 49), with most deaths occurring within 3-5 days after antibiotic therapy was initiated. There was no difference in the case fatality rate between children with penicillin-nonsusceptible and penicillin-susceptible pneumococcal infections; instead; case-fatality rate correlated with severity of illness on admission and presence of underlying disease. CONCLUSIONS: Characterizing groups at risk for invasive pneumococcal disease could aid in the development of preventive programs and increase the benefits from wide use of future conjugated vaccines.     

社区呼吸道感染中肺炎链球菌对常用抗菌药物敏感性

目的了解社区获得性呼吸道感染中肺炎链球菌对常用抗菌药物的体外抗菌活性。方法先用做肺炎链球菌鉴定粗筛,后用全自动细菌分析系统的革兰阳性菌鉴定卡和单克隆乳胶试剂做肺炎链球菌的最终鉴定,药物敏感性试验用微量稀释方法测定其最低抑菌浓度。结果在1997-11~1998-04,1999-11~2000-04和2001-11~2002-04 3个阶段共收集肺炎链球菌271株。在这3个阶段,肺炎链球菌分别为83,101,87株;对青霉素不敏感率分别为9.6%,8.9%和16%,对青霉素耐药率分别为1.2%,2%和8%;对大环类脂类抗生素的敏感性分别为28.9%,39.6%和18.4%。肺炎链球菌对克拉霉素显示高水平耐药。阿其霉素和克拉霉素的交叉耐药率可达98.4%。对左氧氟沙星的耐药率分别为1.2%,6.9%和1.2%; 对复方新诺明的耐药率分别为30.1%,62.4%和66.7%;多重耐药的肺炎链球菌分别为2.4%,3.0%和6.9%。在多重耐药的肺炎链球菌中,以阿齐霉素、复方新诺明和青霉素模式为主,占72.7%(8/11),同时有80%(8/10)对青霉素耐药的肺炎链球菌发生多重耐药;肺炎链球菌对万古霉素未见有耐药株。结论对青霉素耐药的肺炎链球菌有逐年上升的趋势,定期进行细菌耐药性的监测,有助于合理应用抗菌药物。     

肺炎链球菌对大环内酯类抗生素耐药机制研究

目的观察耐大环内酯类肺炎链球菌的耐药表型和基因型。方法用琼脂二倍稀释法测定耐大环内酯类肺炎链球菌对11种抗生素的最低抑菌浓度,耐药表型由红霉素和克林霉素双纸片法初步分型,通过PCR扩增耐药基因ermB和mefA进行基因分型,并测定ermB和mefA基因序列。结果　所有23株肺炎链球菌对大环内酯和克林霉素高度耐药,均表现为内在型耐药,没有发现诱导型耐药和M型耐药。ermB基因在23株肺炎链球菌中均检测到,其中5株同时检测到mefA基因,没有发现仅单一mefA基因阳性的菌株,基因型与耐药表型完全一致。所测ermB和mefA基因序列与基因库收录序列高度一致。 结论ermB基因介导的靶位改变可能是重庆地区肺炎链球菌对大环内酯类抗生素的主要耐药机制。     

How cost effective is switching universal vaccination from PCV10 to PCV13? A case study from a developing country

BackgroundChildren immunization with pneumococcal conjugate vaccine (PCV) had profound public health effects across the globe. Colombian adopted PCV10 universal vaccination, but PCV incremental impact need to be revalued. The objective of this analysis was to estimate the cost-effectiveness of switch to PCV13 versus continue PCV10 in Colombian children.MethodsA complete economic analysis was carried-out assessing potential epidemiological and economic impact of switching from PCV10 to PCV13. Epidemiological information on PCV10 impact was obtained from lab-based epidemiological surveillance on pneumococcal isolates at the Colombian National Institute of Health. Economic inputs were extracted from the literature. Incremental PCV13 effectiveness was based in additional serotypes included. Comparisons among alternatives were evaluated with the Incremental Cost-Effectiveness Ratio (ICER) at a willingness to pay of one GDP per capita (USD$ 6631) per Year of Live Saved (YLS). All costs were reported in 2014USD. Deterministic and probabilistic sensitivity analyses were performed, and 95% confidence interval reported.ResultsAfter four years using PCV10 for universal vaccination on children the Colombian health surveillance system showed a relative increment on non PCV10 isolates. To change from PCV10 to PCV13 would avoid 587 (CI95% −49–1008) ambulatory Rx community-acquired pneumoniae (CAP), 1622 (CI95% 591–2343) Inpatient RxCAP, 10 (CI 95% 6–11) pneumococcal meningitis, and 79 (CI95% 76–98) deaths. ICER per YLS was USD$ 2319 (CI95% Dominated – USD$ 4225) for Keep-PCV10 and USD$ 1771 (CI95% USD$ 1285–9884) for Switch-to PCV13. In spite of its cost-effectiveness Keep-PCV10 is an extended dominated alternative and Switch-to PCV13 would be preferred. Results are robust to parameters changes in the sensitivity analyses.ConclusionA national immunization strategy based in Switch-to PCV13 was found to be good value for money and prevent additional burden of pneumococcal disease saving additional treatment costs, when compared with to Keep-PCV10 in Colombia, however additional criteria to decision making must be taken into account.     

An innovative quaternary ammonium methacrylate polymer can provide improved antimicrobial properties for a dental adhesive system

A quaternary ammonium methacrylate polymer (QAMP) with antimicrobial potential was synthesized. The resulting product (QAMP) was characterized by FTIR spectroscopy, NMR spectroscopy, visible spectrophotometry, XRPD and TGA. The in vitro susceptibility tests against Streptococcus mutans of QAMP were investigated prior and after incorporation into a commercial adhesive system (Clearfil? SE Bond). The release of quaternary ammonium compounds from the experimental adhesive system (Clearfil? SE Bond?+?5% QAMP) was performed during 1, 7, 14, 21 and 30 days. Spectroscopic data confirmed that QAMP was successfully obtained. Thermogravimetric analysis indicated that QAMP was heat stable. Prior incorporation into the adhesive system, QAMP revealed an inhibition halo of 18.33?±?0.6?mm. By agar disk diffusion test, Clearfil? SE Bond containing 5% QAMP presented an inhibition halo (16.67?±?1.5?mm) similar to Clearfil? Protect Bond (positive control, 17.00?±?1.7, p?=?0.815) and significantly higher than Clearfil? SE Bond (negative control, 11.00?±?1.0, p?=?0.006). The minimum inhibitory/bactericidal concentrations for Clearfil? SE Bond containing 5% QAMP were 20?μL?mL^?1. The release of quaternary ammonium compounds from the experimental adhesive containing QAMP was very low (5.1%) when compared to Clearfil? Protect Bond that released 47.2% of its quaternary ammonium monomer (MDPB) after 30 days. The QAMP can offer enhanced antimicrobial properties for self-etching adhesive systems.     

Relevance of O-acetyl and phosphoglycerol groups for the antigenicity of Streptococcus pneumoniae serotype 18C capsular polysaccharide

Capsular polysaccharides are important virulence factors of Streptococcus pneumoniae. The polysaccharide has been used as a component of vaccines against pneumococcal diseases either as plain polysaccharide or better conjugated to a protein. The last one is the vaccine of choice to target child protection. The immune responses depend on several polysaccharide physicochemical properties that can be affected during either purification or modification in the case of conjugate vaccines. In serotype 18C, the repeating unit has a complex structure having a branched pentasaccharide with two apparently labile subtituents: glycerol-phosphate and O-acetyl group. The loss of these groups may potentially reduce the ability of the 18C polysaccharide to induce the desired immune response. Therefore, the relationship of both groups with the antigenicity and immunogenicity of 18C capsular polysaccharide is explored. It is shown that glycerol-phosphate must be preserved for conserving adequate antigenicity of the 18C capsular polysaccharide. At the same time, it was proved that O-acetyl groups do not play any role for the antigenicity and immunogenicity.     

Transmission of Streptococcus equi Subspecies zooepidemicus Infection from Horses to Humans

Streptococcus equi subspecies zooepidemicus (S. zooepidemicus) is a zoonotic pathogen for persons in contact with horses. In horses, S. zooepidemicus is an opportunistic pathogen, but human infections associated with S. zooepidemicus are often severe. Within 6 months in 2011, 3 unrelated cases of severe, disseminated S. zooepidemicus infection occurred in men working with horses in eastern Finland. To clarify the pathogen’s epidemiology, we describe the clinical features of the infection in 3 patients and compare the S. zooepidemicus isolates from the human cases with S. zooepidemicus isolates from horses. The isolates were analyzed by using pulsed-field gel electrophoresis, multilocus sequence typing, and sequencing of the szP gene. Molecular typing methods showed that human and equine isolates were identical or closely related. These results emphasize that S. zooepidemicus transmitted from horses can lead to severe infections in humans. As leisure and professional equine sports continue to grow, this infection should be recognized as an emerging zoonosis.     

Safety and immunogenicity of a prototype recombinant alpha-like protein subunit vaccine (GBS-NN) against Group B Streptococcus in a randomised placebo-controlled double-blind phase 1 trial in healthy adult women

BackgroundGroup B Streptococcus (GBS) is the leading cause of life-threatening infections in new-borns and may cause invasive disease, stillbirth and preterm delivery during pregnancy. While no licensed vaccine exists, maternal immunization might protect against neonatal disease and adverse pregnancy outcomes. We assessed the safety and immunogenicity of a prototype vaccine consisting of the fused N-terminal domains of the AlphaC and Rib surface proteins of GBS (GBS-NN).MethodsGBS-NN was tested in a randomised, double-blind, placebo-controlled, parallel group, phase I study, in healthy non-pregnant women. A dose-escalation phase, with two doses, four weeks apart, of 10, 50 or 250 µg, administered with or without aluminium hydroxide, was initially assessed (n = 60). This was followed by a dose-confirmation study, where one dose of 100 µg adjuvanted GBS-NN was compared with two doses of either 50 or 100 µg adjuvanted GBS-NN, again administered with four weeks interval between the doses (n = 180). Safety and immunogenicity were monitored for one year.ResultsGBS-NN was well tolerated with some, mostly mild, injection site reactions observed. Adjuvant significantly increased antibody concentrations and the response was boosted by a second dose. The IgG GMCs remained strongly elevated during the whole one-year duration of the study. Maximal responses occurred after two 50 µg doses, resulting in IgG GMC of 16.9 µg/ml at the primary immunological endpoint, twelve weeks after the first dose. For this regimen, 100% and 89% of the subjects achieved antibody levels above the arbitrary thresholds of 1 and 4 µg/ml, respectively. The added beneficial effect of a second dose was most pronounced for subjects with pre-existing IgG levels below the median of the entire cohort.ConclusionThe prototype GBS-NN vaccine was found to be well tolerated and highly immunogenic with an optimal regimen of two doses of 50 µg in the presence of adjuvant. Further development of a maternal vaccine based on the N-terminal domains of the alpha-like protein family of GBS is warranted (NCT02459262).     

绍兴地区肺炎链球菌的血清型和耐药性

目的:调查绍兴地区流行肺炎链球菌的血清型和耐药性,对不同来源的菌株进行比较,计算PCV7的覆盖率,为临床用药提供指导。方法:收集105株不同样本来源的肺炎链球菌,使用Pneumotest-latex鉴定血清型,统计耐药性,并研究两者之间关系。结果:105株肺炎链球菌,青霉素不敏感仅1株咽拭子分离菌,红霉素、克林霉素耐药率为99.3%,未检到万古霉素、左氧氟沙星耐药株,复方SMZ、四环素、利福平、氯霉素的耐药率分别为77.9%、86.2%、5.1%、10.6%。主要检出的血清组/型为19和23,占所有菌株的47.6%(49/103),PCV疫苗覆盖率为62.1%。结论:不同样本来源的肺炎链球菌的流行血清型和耐药性差异有统计学意义,眼部分离肺炎链球菌较其他部位分离株耐药程度低,PCV7覆盖率低,需长期监测。