Streptococcus pneumoniae bacteraemia in children

Occult bacteraemia is the most frequent invasive disease caused by Streptococcus pneumoniae in children less than 3 years of age. Despite the relative frequency of this infection, its management is still a challenging task for paediatricians because fever is often the only symptom and a considerable overlap exists in the clinical presentation of children with fever without a focus due to viral illness and children with occult bacteraemia. Management protocols take into account the age of the patient, the clinical score for severity and the results of laboratory tests such as the white blood cell count, the C-reactive protein and the blood procalcitonin level in order to define accurately who will benefit from an antibiotic treatment. Despite appropriate healthcare facilities and access to care the case fatality rate in developed countries is around 9% in children aged less than 1 year. Prevention with the 7-valent conjugate vaccine against S. pneumoniae will decrease morbidity and mortality associated with invasive disease due to these bacteria. However, replacement by non-vaccine serotypes has been noted in countries where the vaccine is widely used and this concern needs to be monitored carefully over the next few years.     

Predicting the future Streptococcus pneumoniae resistance landscape

Streptococcus pneumoniae resistance to antibiotics is considered a public health problem, and yet the link between year-to-year increases in resistance and antimicrobial consumption has been difficult to prove. Mathematical models and epidemiological studies have shown that there is no linear relationship between consumption and resistance, and that increasing resistance is caused by the removal of susceptible strains from the population. Pneumococcal conjugate vaccine has also been shown to have an impact over resistance. A model that relates resistance with the cumulative consumption of antibiotics over time explains low resistance rates in countries such as Germany and plateaus in resistance in the US. Moreover, understanding this temporal relationship allows us to predict that if the cumulative consumption stabilizes so will the resistance rates.     

高效毛细管电泳法测定头孢克洛干混悬剂中头孢克洛的含量

目的:测定头孢克洛干混悬剂中头孢克洛的含量.方法:采用高效毛细管电泳法.毛细管柱(60cm×75μm),运行缓冲液30mmol·L-1硼砂(pH 9.2),高压进样5s,分离电压12kV,温度为25℃,检测波长为254nm,地塞米松磷酸钠为内标.结果:头孢克洛在8～40μg·mL-1浓度范围内线性关系良好(r=0.999 8),平均回收率为 99.18% (n=5,RSD=1.69%).结论:本法简单、快捷、灵敏.     

Call for the international adoption of microbiological breakpoints for fluoroquinolones and Streptococcus pneumoniae

The use of current Clinical and Laboratory Standards Institute levofloxacin breakpoints for assessing fluoroquinolone resistance in Streptococcus pneumoniae is inadequate for detecting isolates possessing first-step parC mutations. Consequently, the risk for development of fluoroquinolone resistance is greatly underestimated. Adopting microbiological breakpoints for fluoroquinolones and S. pneumoniae, where parC mutations are rare in susceptible isolates, more accurately describes the emergence of resistance and may help to prevent a number of future fluoroquinolone treatment failures. Additionally, we propose that the use of a second fluoroquinolone marker, such as ciprofloxacin, offers the best prediction for detecting an isolate possessing a first-step parC mutation.     

Novel approaches to fight Streptococcus pneumoniae

Streptococcus pneumoniae affects millions of people worldwide. It is responsible for a wide spectrum of serious illnesses such as pneumonia, meningitis and bacteraemia. The highest rate of pneumococcal disease (and the highest mortality) occurs in young children, as well as in the elderly and the immunocompromised patients. Identification of S. pneumoniae in diagnostic procedures may significantly improve thanks to the descripion of new PCR-derived techniques. Vaccination based on the polysaccharidic capsule, together with benzylpenicillin-derived drugs, constitute the current choices to tackle pneumococcal diseases. However, the wide serotype diversity of S. pneumoniae and the emergence of antibiotic-resistant strains is fostering the development of new methods to fight this microorganism. In this sense, patents documenting the use of novel antibiotics of the fluoroquinolone or tetracycline families have recently been described. Moreover, surface-associated proteins are receiving an increasingly special attention, as they are synthesized by most pneumococcal strains and play an important role in virulence. New patented protein-based vaccines take into consideration these polypeptides. In this article we present the main relevant characteristics of this pathogen and review the most recent methods that have been patented for the prevention, diagnostic and treatment of the pneumococcal diseases.     

324株儿童感染肺炎链球菌耐药情况的分析

目的了解本院儿童感染肺炎链球菌(SP)的耐药情况。方法采集本院2007年1月至2008年6月324株SP,纸片扩散法(K-B法)进行抗菌药物敏感实验,E-test法测最低抑菌浓度(MIC)。结果324株肺炎链球菌耐药率,阿莫西林/棒酸为17.90%,万古霉素为3.09%,阿奇霉素为96.91%,复方新诺明为70.37%,美罗培南为0.62%,氨苄西林为25.31%,青霉素为94.75%,头孢曲松为10.19%,氧氟沙星为14.20%,头孢克洛为53.09%,氯霉素为3.70%,红霉素为95.37%。结论南京地区儿童感染SP,青霉素、阿奇霉素、红霉素耐药率高,耐药情况严峻。     

儿童肺炎链球菌性疾病的治疗

肺炎链球菌性疾病(尤其侵袭性肺炎链球菌性疾病)是5岁以下儿童较常见的感染性疾病,肺炎链球菌对抗菌药物的耐药性给临床治疗带来新的挑战.本文综述儿科肺炎链球菌性疾病、肺炎链球菌的耐药现状,并重点评论肺炎链球菌性疾病的治疗策略,包括肺炎链球菌性肺炎、中耳炎、鼻窦炎、脑膜炎和其他侵袭性肺炎链球菌性疾病,积极防治肺炎链球菌性疾病...     

Clinical impact of cefepime breakpoint in patients with carbapenem-resistant Klebsiella pneumoniae bacteraemia

The application of cefepime breakpoint for carbapenem-resistant Klebsiella pneumoniae (CRKP) bacteraemia has not been explored. Adult cases of monomicrobial bloodstream infection (BSI) caused by cefepime-susceptible [minimum inhibitory concentration (MIC) ≤8 mg/L] K. pneumoniae isolates with carbapenem resistance between 2010 and 2015 were reviewed. Patients treated with cefepime were compared with those treated by other active agents using a propensity score-matched analysis to assess therapeutic effectiveness. The primary endpoint was 30-day crude mortality. A total of 114 patients experienced cefepime-susceptible CRKP bacteraemia and 40 (35.1%) died during hospitalisation. A total of 33 patients (28.9%) received cefepime therapy. Fifteen patients (13.2%) had BSI due to carbapenemase-producing isolates, and 86.7% (13/15) of carbapenemase-producing isolates were classified as cefepime susceptible dose-dependent (SDD). In the multivariate logistic regression analysis, 30-day mortality was independently associated with the presence of a critical illness [adjusted odds ratio (aOR) = 12.89, 95% confidence interval (CI) 3.88–42.83; P < 0.001], pneumonia (aOR = 5.97, 95% CI 1.65–21.76; P = 0.007) and rapidly fatal underlying disease (aOR = 6.43, 95% CI 1.30–31.09; P = 0.02). In contrast, cefepime-based therapy (aOR = 0.03, 95% CI 0.003–0.38; P = 0.006) and combination therapy (aOR = 0.09, 95% CI 0.02–0.36; P = 0.001) were protective against a fatal outcome. Based on current breakpoints for Enterobacterales, cefepime therapy was not associated with an unfavourable outcome for CRKP BSI with MIC-based dosing strategies. However, the susceptibility result of SDD to cefepime should alert clinicians for possible therapeutic failure.     

肺炎链球菌的耐药性监测

肺炎链球菌耐药率不断上升,监测其耐药性并掌握耐药特征,有助于指导临床合理选药及控制肺炎链球菌耐药株流行.本文综述肺炎链球菌的耐药现状、相关机制及监测方法.     

Drug-resistant Streptococcus pneumoniae in the Lebanon: implications for presumptive therapy.

A total of 50 consecutive clinical isolates of Streptococcus pneumoniae, collected between 1996 and 1998, were tested against six antimicrobial agents using the E-test. The percentages of fully resistant (R) and intermediately-R strains, respectively, were: benzyl penicillin 18 and 38%, amoxycillin-clavulanate 6 and 12%, cefuroxime 22 and 16%, ceftriaxone 2 and 16%, and clarithromycin 10%. Fully and or intermediately multidrug-resistance (two or more drugs) was seen in 44% of the isolates, 18% being fully resistant. The MIC breakpoint for cefaclor is not defined by the National Committee for Clinical Laboratory Standards (NCCLS) but MICs showed that: 76% of the isolates had an MIC of ≤8 mg/l, 4% had an MIC of 16 mg/l and 20% had an MIC of ≥32 mg/l. There was agreement between the E-test Pen MIC results and the 1 μg oxacillin (oxa) disk diffusion screen test for the 22 susceptible and the nine fully R strains but not for the 19 strains with Pen MICs between 0.1 and 1 mg/l; this shows the importance of MIC determination in such isolates. Penicillin and multiply antibiotic-resistant pneumococci are spreading in Lebanon, emphasizing the necessity to reconsider current treatment regimens in this country.     

Investigation of the antibacterial activity of faropenem against Streptococcus pneumoniae

We evaluated the antibacterial activity of faropenem against penicillin-susceptible Streptococcus pneumoniae (PSSP) and penicillin-resistant S. pneumoniae (PRSP). It was shown that the minimum inhibitory concentrations against 90% of the clinically isolated strains (MIC90) of faropenem, penicillin G, cefaclor, cefcapene, and cefditoren against PSSP were 0.032, 0.063, 2, 0.25, and 0.125 micrograms/ml, respectively. While those against PRSP were 0.5, 2, > 128, 1, and 1 micrograms/ml, respectively. Furthermore, we evaluated the bactericidal activity, at the level of 1/4, 1, and 4 MIC, of faropenem and the above four reference antibacterial agents against PSSP and PRSP. Against PSSP No. 127, a sensitive strain to both penicillin G and cefcapene, faropenem showed almost the same bactericidal activity as those of reference agents. Against PSSP No. 108, a penicillin-susceptible and cephem-resistant strain, and PRSP No. 57, a resistant strain to both of penicillin and cephem, faropenem of 1 MIC showed bactericidal activity, but reference agents needed 4 MIC to show bactericidal activity.     

Multiple antibiotic resistance in Streptococcus pneumoniae.

Streptococcus pneumoniae remains a major pathogen responsible for high morbidity and mortality in both the developed and developing world. During the last few years there has been a dramatic increase in the incidence of penicillin-resistant and multiply antibiotic-resistant pneumococci, and the emergence of isolates with high-level resistance to extended-spectrum cephalosporins. In several countries, 50-80% of pneumococcal isolates, including the great majority of isolates of the serotypes associated with disease and carriage in children, are penicillin-resistant. Penicillin-resistant pneumococci are diverse, but in several countries successful highly penicillin-resistant clones (which in most cases are resistant also to tetracycline, chloramphenicol, and cotrimoxazole, and increasingly to erythromycin) have emerged, and some of these have spread globally. The effect of antibiotic resistance on the clinical outcome of otitis media, pneumonia and meningitis, and the potential of the new conjugate vaccines for controlling pneumococcal disease, are discussed.     

A survey of isolates of Streptococcus pneumoniae.

Over eight months 130 isolates of Streptococcus pneumoniae were examined for sensitivity to penicillin, tetracycline, cephalosporin and co-trimoxozole. Except in one doubtful case all isolates were sensitive to penicillin. All were sensitive to cephalosporin. 6.9 percent is isolates were resistant to co-trimoxozole. It is suggested that penicillin remains the drug of choice in the treatment of pneumococcal infections.     

Antibiotic susceptibility of Streptococcus pneumoniae in New Zealand

AIMS: To determine the current antibiotic susceptibility patterns of Streptococcus pneumoniae from four centres in New Zealand. METHODS: Over a six-month period in 1997, 386 consecutive clinical isolates of S pneumoniae were collected by four laboratories (Auckland, Wellington, Hamilton and Christchurch) from general practice or inpatients. Susceptibility testing for seven antibiotics was performed by each centre using the Etest. RESULTS: Eighty-three-percent of isolates were penicillin susceptible, 12% showed intermediate resistance to penicillin and 5% were penicillin resistant. Overall, 93 and 91% of isolates were susceptible to amoxicillin/clavulanic acid and ceftriaxone, respectively. Erythromycin and tetracycline had similar rates of susceptibility (88 and 87%, respectively). Resistance to cotrimoxazole was common, with only 57% of isolates susceptible to this combination. No National Committee for Clinical Laboratory Standard (NCCLS) breakpoints were available for cefaclor to allow interpretation of the minimum inhibitory concentration data for this agent. Wellington had lower resistance rates than Auckland, Christchurch and Hamilton. Isolates from children had consistently higher resistance rates (two- to five-fold greater for beta-lactams and 1.2 to 1.3-fold for other agents) compared with isolates from adult patients. CONCLUSIONS: Resistance to multiple antibiotics among S pneumoniae is now evident in New Zealand, although rates varied between study centres. The overall rate of penicillin resistance is 5%, which is similar to that observed in many European and US cities but lower than the rates reported in badly affected areas (> 30%). These data suggest that amoxicillin (+/- clavulanic acid), erythromycin or tetracycline are appropriate agents for empirical use in less serious community acquired infections when S pneumoniae is suspected. Ceftriaxone, with or without vancomycin, should be considered in the empirical treatment of invasive, disease until sensitivities are known.     

Epidemiological analysis of Streptococcus pneumoniae in Gifu prefecture

Since antimicrobial resistance in Streptococcus pneumoniae become serious problem, we have conducted the epidemiological analysis of Streptococcus pneumoniae in Gifu prefecture. We have investigated the mutations of penicillin-binding protein (PBP) cording genes, the mutations of macrolide-resistant cording genes, and antimicrobial susceptibility using broth microdilution method, for 345 strains isolated from clinical specimens between May 2006 and July 2006 at 12 clinical facilities of 5 medical area. The ratio of penicillin-susceptible S. pneumoniae (gPSSP), penicillin-intermediate S. pneumoniae (gPISP), and penicillin-resistant S. pneumoniae (gPRSP), which were judged by molecular techniques, were 7.2%, 53.5%, and 39.4%, respectively. Only 1 gPSSP strain was isolated from children under three years old. There have been regional differences of the isolation rate of gPRSP between Gifu/Chuno area (55-60%) and Tono/Hida area (23-32%) in second- or third-medical facilities. The isolation rate of PBP mutation genes, pbp2x, pbp1a and pbp2b, were 92.8%, 52.5% and 53.3%, respectively. The isolation rate of macrolide-resistant cording genes, mefA only, ermB only, and both mefA and ermB, were 30%, 50% and 8%, respectively. The strains of S. pneumoniae with both mefA and ermB mutations, increased from 4% in 2002 to 8% in 2006. The antimicrobial susceptibility of S. pneumoniae to penicillin G (PCG) showed two peaks around 0.03 and 1 microg/mL, and 89% of S. pneumoniae with minimum inhibitory concentration (MIC) value 1 microg/mL was gPRSP. The MIC values of PCG against 69% strains of gPRSP distributed between 0.25 and 1 microg/mL. There have been the decreased tendency for the differences among medical facilities in penicillin resistant strains. Although cefditoren showed the most effective antimicrobial activity in oral cephems tested, there have been the strains with MIC value of over 1 microg/mL. The MIC90 of panipenem was 0.125 microg/mL, which was the best antimicrobial activity in carbapenems. The resistant rates of clarithromycin and azithromycin were 85% and 84%, respectively. The strains with the gene mutation of ermB have showed resistant to clindamycin. The MIC90 of tosufloxacin was 0.25 microg/mL, which was the best antimicrobial activity in quinolones. We have detected 4 levofloxacin highly resistant S. pneumoniae, of which MIC value was over 32 microg/mL. Also, we have encountered the episode of the spread of S. pneumoniae in one family, which was clarified by scientific approach.     

Epidemiology of Streptococcus pneumoniae isolates in Gifu Prefecture

We analyzed Streptococcus pneumoniae isolates confirmed by direct PCR in Gifu prefecture between May 2002 and August 2002. We analyzed isolates of 254 strains from 6 hospitals to determine antibiotic susceptibility, genotype of penicillin-binding protein (PBP) genes and macrolide resistant genes, and the serotypes distribution of isolates from Matsubara Otorhinolaryngology Clinic. Isolates in which abnormal PBP genes of pbp1a, pbp2x, and pbp2b were identified by PCR were classified based on PCR results as follows; (i) penicillin-susceptible (PSSP) with 3 normal PBP genes, (ii) penicillin-intermediate (PISP) with an abnormal pbp2x, (iii) PISP with an abnormal php2b, (iv) PISP with abnormal pbp2x and pbp2b, (v) PISP with abnormal pbpla and pbp2x, (vi) penicillin-resistant (PRSP) with 3 abnormal PBP genes. The overall incidence of PRSP, PISP and PSSP was 121 (49%), 109 (42%) and 24 (9%), respectively, and there was a significant difference among some hospitals (p<0.05). However, there was no significant difference among the hospitals for the incidence of abnormal macrolide-resistant genes (mefA, ermB). Panipenem showed an excellent antimicrobial activity for injectable carbapenems against PRSP, following biapenem, imipenem, and meropenem. Cefditoren (CDTR) showed an excellent antimicrobial activity for oral cephalosporins against PRSP, following cefteram and cefcapene. Interestingly, there were 2 and 3 strains on MIC of CDTR for 8 and 4 microg/mL, respectively. The prevalent pneumococcal serotypes of isolates in Matsubara Clinic were 6 (17/55), following by 40 (8/55), 9 (6/5) and 15 (5/55). The endemic strains were observed in this study using pulsed field gel electrophoresis. These findings suggest the needs to continue the surveillance of bacterial resistance not only in the nationwide but also in the distict.     

肺炎球菌疫苗生产菌种肺炎链球菌种子批质量控制

肺炎球菌多糖疫苗或多糖蛋白结合疫苗在预防肺炎球菌性疾病中发挥着重要的作用。肺炎链球菌是肺炎球菌疫苗研制、生产的重要原材料,也是国家重要的战略储备资源,其质量直接或间接影响终产品肺炎球菌疫苗的质量、安全和效力。因此,严格控制肺炎球菌疫苗生产用肺炎链球菌的质量至关重要。本文对肺炎球菌疫苗生产用肺炎链球菌种子批的传统检定方法和分子生物学检定方法(16S rRNA序列测定、基于PCR的血清分型、多位点序列分型、脉冲场凝胶电泳分型和全基因组序列测序)进行概述,并对这些方法的优缺点进行讨论,以期为完善生产用肺炎链球菌种的质控方法和质量标准提供帮助。