Antimicrobial susceptibility profiles associated with bacterial meningitis among children: a referral hospital-based study in Iran

Bacterial meningitis continues to be associated with high morbidity and mortality rate worldwide, especially in the pediatric age group. This study was performed to identify the microbial etiologies of meningitis among 31 children, who were admitted in the Emergency Ward of a referral pediatric hospital in Iran. Culture identification showed that Streptococcus pneumoniae (12 subjects), Haemophilus influenzae (11 subjects) were the most common bacteria, followed by Escherichia coli (7 cases) and Neisseria meningitidis (only one case). Antibiotic susceptibility tests revealed that vancomycin had the best effect on S. pneumoniae in comparison with other antibiotics, whereas H. influenzae and E. coli were more susceptible to ceftriaxone, ceftazidime, and ceftizoxime than other antibiotics. In conclusion, despite the advances in antibiotic therapy and vaccine development, bacterial meningitis still is a health problem. S. pneumoniae, H. influenzae, and N. meningitidis are the main sources of bacterial meningitis, but other organisms such as E. coli should also be suspected, when a case is admitted to a referral pediatric hospital.     

114株肺炎链球菌的临床分布及药敏分析

目的波市妇女儿童医院肺炎链球菌的临床分布和耐药情况,为临床合理用药提供依据。方法对该院2009年6月1日至2011年3月31日期间分离的114株肺炎链球菌进行分析,菌株鉴定采用法国生物梅里埃公司的VITEK60分析仪,药敏试验采用K-B法,用参考菌株做质量控制。结果该院分离的肺炎链球菌主要来自儿童（84.21%）,标本来源主要是痰液（61.4%）,其次是血液（9.65%）,其他（28.95%）。肺炎链球菌的耐药率：林可霉素92.19%,红霉素90.12%,青霉素G85.53%,左旋氧氟沙星20.24%,氨苄西林16.67%,头孢唑啉8.7%,头孢曲松5.8%,头孢噻肟4.11%,万古霉素0%,氨苄西林/舒巴坦0%,哌拉西林/他唑巴坦0%。结论宁波市妇女儿童医院肺炎链球菌对某些药物的耐药率很高,有必要对其进行耐药率监测,指导临床合理选择抗菌药物。     

Single tube real time PCR for detection of Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydophila pneumoniae and Legionella pneumophila from clinical samples of CAP

We designed a multiplex real time PCR for rapid, sensitive and specific detection of Streptococcus pneumoniae, Legionella pneumophila, Chlamydophila pneumoniae and Mycoplasma pneumoniae. The study cases consisted of 129 patients with community acquired pneumonia (CAP). Bacteriological techniques were implemented for detection of the cultivable organisms. DNA were extracted from sputa, throat swabs, bronchoalveolar lavages and tracheal aspirates and used as templates in real time PCR. The primers and probes were designed for cbpA (S. pneumoniae), p1adhesin (M. pneumoniae), mip (L. pneumophila) and ompA (C. pneumoniae). After optimization of real time PCR for every organism, the experiments were continued in multiplex in a single tube. Of 129 CAP specimens, the positive cultures included 14 (10.85%) for S. pneumoniae, 9 (6.98%) for L. pneumophila and 3 (2.33%) for M. pneumoniae. Four specimens (3.10%) were positive for C. pneumoniae by real time PCR. The sensitivity of our real time PCR was 100% for all selected bacteria. The specificity of the test was 98.26%, 98.34%, 100% and 100% for S. pneumoniae, L. pneumophila, M. pneumoniae and C. pneumoniae, respectively. This is the first report on the use of multiplex real time PCR for detection of CAP patients in the Middle East. The method covers more than 90% of the bacterial pathogens causing CAP.     

Serotype distribution of Streptococcus pneumoniae in north-western Greece and implications for a vaccination programme

Serotypes and antibiotic sensitivities were determined for 338 strains of Streptococcus pneumoniae from children of north-western Greece with invasive pneumococcal disease (IPD), acute otitis media (AOM) and nasopharyngeal carriage. The most common serotypes among the isolates from IPD were 14 and 19F, while 3, 19F, 9V and 14 were the major cause of AOM. In these groups, the heptavalent conjugate vaccine for pneumococci (7vPCV) seems to cover 90.5% of the serotypes isolated from children less than 2 years old. Serotypes 23F and 6B were the most prevalent in carrier strains. Overall, 23.7% of the isolates were penicillin nonsusceptible (PNS), 97% were fully susceptible to cefotaxime, 29% were resistant to erythromycin, 11.2% to co-trimoxazole and 1.2% to clindamycin.     

Community-acquired pneumonia in adults.

Although the frequency of community-acquired pneumonia caused by Streptococcus pneumoniae continues to be high, studies show that Mycoplasma pneumoniae, Chlamydia pneumoniae, or Legionella pneumophila are the etiologic agents in 20% to 40% of community-acquired pneumonia in adults. The clinical presentation of pneumonia caused by these organisms may be indistinguishable from pneumonia due to S pneumoniae. Separation of cases of pneumonia due to S pneumoniae as typical and that caused by M pneumoniae, C pneumoniae, or L pneumophila as atypical is unwarranted and unhelpful in planning therapy. As many as 35% to 50% of patients do not have an etiologic agent identified. Community-acquired pneumonia can have high morbidity and mortality in patients who are older, have underlying lung disease, diabetes mellitus, or other comorbid conditions, or who have decreased immune function regardless of the specific etiologic agent. In choosing appropriate empiric antimicrobial therapy in hosts who are not immunocompromised, erythromycin and other macrolide antibiotics have the advantage of being effective against a wide range of pathogens likely to be encountered, including S pneumoniae, M pneumoniae, and L pneumophila, and of having some benefit against C pneumoniae. In other patients, the selection of antibiotic therapy can be based on age, clinical suspicion, epidemiologic data, and laboratory test results. Antimicrobial therapy can be directed at specific organisms when and if they are identified.     

Nasal carriage of Streptococcus pneumoniae among Hungarian children before the wide use of the conjugate vaccine

Streptococcus pneumoniae is responsible for a significant amount of morbidity and mortality worldwide, especially among children <5 years. Healthy carriers are the most important sources of infections and the carriage also peaks in the first years of life, especially among children attending communities. In this study, for the first time in Hungary, we surveyed the nasal carriage of healthy children, just before the use of the conjugate vaccine started increasing.Nasal specimens of 358 children were cultured and pneumococci isolated. The strains were serotyped with antisera and PCR, genotyped by PFGE and their antibiotic sensitivity determined by agar dilution method.The carriage rate was 37.71%. The isolates were sensitive to most tested antibiotics, except for macrolides. In this cohort of specimens still the widespread, so-called "pediatric serotypes" dominated (14, 19F, 23F, 6A, 6B in ranking order), but three of the previously rare types: 15B, 11A and 13 were represented already by 21.5% of all strains and also a few other rare non-vaccine types (e.g. 10A or 37) were detected.The calculated vaccine coverage was 55.6% for PCV-7, 69.6% for PCV-13 and 86.7% for Pneumovax. In this cohort, only 15.9% of the children (n = 57) were vaccinated. The carriage rate of PCV-7 vaccinated children was significantly lower (30.4%) than that of the non-vaccinated group (39.2%). The clonality of the isolates was significant within each group, revealing the extensive bacterium exchange among children.     

The synthesis and antibacterial activity of totarol derivatives. Part 3: Modification of ring-B

Ring-B derivatization of totarol (1) afforded the series of compounds 2-22 which were screened in vitro against: beta-lactamase-positive and high level gentamycin-resistant Enterococcus faecalis, penicillin-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), and multiresistant Klebsiella pneumoniae. Several of the derivatives retained much of the antibacterial activity of totatol against the first three of these organisms (all gram-positive), but none was more active. The gram-negative Klebsiella was resistant to all compounds examined. Totarol (1) was shown to uncouple oxidative phosphorylation in isolated mitochondria at 50 microM.     

儿童呼吸道肺炎链球菌和金黄色萄萄球菌的耐药性研究

目的了解儿童感染肺炎链球菌和金黄色萄萄球菌耐药情况,为临床合理用药提供理论依据。方法对年龄为1个月～12岁的上呼吸道感染的儿童鼻咽分泌物或痰进行培养,分离肺炎链球菌和金黄色萄萄球菌;采用纸片扩散法及E-test法对分离株进行常用的10种抗生素敏感性检测。结果从2 250例呼吸道感染儿童鼻咽部、痰液分离出肺炎链球菌共120株,金黄色葡萄球菌共151株。120株肺炎链球菌对常用抗菌药物耐药率分别为青霉素41.7%(50/120)、苯唑西林26.7%(32/120)、头孢曲松9.2%(11/120)、红霉素95.8%(115/120)、克林霉素90.0%(108/120)、四环素70.8%(85/120)、氯霉素6.7%(8/120)、利福平0.8%(1/120)和氧氟沙星0.8%(1/120),肺炎链球菌青霉素不敏感株对β-内酰胺酶类耐药率明显高于青霉素敏感株。151株金黄色葡萄球菌中对常用抗菌药物耐药率分别为青霉素97.4%(147/151)、苯唑西林9.9%(15/151)、头孢曲松9.3%(14/151),对红霉素52.3%(79/151)、四环素31.8%(48/151)、克林霉素24.5%(37/151)、氯霉素9.9%(15/151)、氧氟沙星3.3%(5/151)和利福平2.0%(3/151)。未检出耐万古霉素菌株。结论肺炎链球菌对红霉素、克林霉素高度耐药;而金黄色葡萄球菌对青霉素高度耐药,临床应尽量减少此类药物的经验性用药,依据药敏结果选择抗菌药物进行治疗。     

Streptococcus pneumoniae nasopharyngeal colonization in young healthy children: rate of carriage,serotype distribution,and antibiotic resistance

The nasopharyngeal colonization rate of Streptococcus pneumoniae and its antibiotic susceptibility was determined in a given population of 317 young children (ages 1-7 years) in the area of Bari, Italy. 18.29% of the cultures were positive for S. pneumoniae. 8.62% of the strains were intermediately resistant to penicillin. Erythromycin-(65.51%) and cotrimoxazole-(17.24%) resistance was also observed whereas all the strains resulted uniformely susceptible to cefotaxime and ceftriaxone. The high rate of nasopharyngeal carriage of Streptococcus pneumoniae along with the resistance to antibiotics widely used in the community suggests the importance of epidemiological surveillance as well as the application of new vaccine strategies.     

Biliary microflora of patients with chronic pancreatitis

Data on the contamination of bile specimens (1997 and 2001, 205 specimens, 137 cultures), examined in the Laboratory of Clinical Microbiology of the Vladimirsky Regional Research Clinical Institute, as well as data on the microflora composition in 40 specimens of bile, obtained from patients with clinically diagnosed chronic pancreatitis at the stage of exacerbation, are presented. Out of 40 specimens of bile 54 cultures of microorganisms were isolated; of these, 33.3% were bacteria of the genus Staphylococcus, Gram negative bacilli took the second place in occurrence (27.8%) and the third place belonged to bacteria of the genus Streptococcus (18.5%). The antibiotic sensitivity of the isolated microorganisms is characterized.     

Burden of pneumonia and meningitis caused by Streptococcus pneumoniae in China among children under 5 years of age: a systematic literature review

BACKGROUND AND METHODS: To understand the burden and epidemiology of Streptococcus pneumoniae disease among children between 1 and 59 months of age in China, we conducted a review of literature published between 1980 and 2008 applying standardized algorithms. Because of the absence of population-based surveillance for pneumococcal disease (PD), we identified all-cause pneumonia, bacteremia and meningitis burden, syndromes most commonly associated with S. pneumoniae, and applied the proportion of disease attributable to S. pneumoniae from studies that determined the etiology of these three syndromes to calculate PD burden. Because of the microbiologic difficulties in identifying S. pneumoniae-attributable pneumonia which likely underestimates the pneumonia burden, we also used the proportion obtained from vaccine efficacy trials. RESULTS: Between 1980 and 2008, there were 12,815 cases/100,000/year of all-cause pneumonia among children between 1 month and 59 months, with 526 deaths/100,000 annually. There were 14 meningitis cases/100,000/year. We estimate that as of 2000, there were 260,768 (113,000 to 582,382) and 902 (114-4,463) cases of pneumococcal pneumonia and meningitis, respectively with 10,703 (4,638-23,904) and 75 (9-370) pneumococcal pneumonia and meningitis deaths, respectively. Pneumococcal pneumonia cases and deaths were more than two-fold higher, 695,382 (173,845-1,216,918) and 28,542 (7,136-49,949), respectively, when parameters from efficacy trials were used. Serotypes 19F, 19A and 14 were the most common serotypes obtained from pneumonia/meningitis patients. Currently available vaccines are expected to cover 79.5% to 88.4% of the prevalent serotypes. With high antibiotic resistance, introducing pneumococcal vaccines to the routine immunization program should be considered in China. Population-based studies are warranted.     

Etiology and Incidence of Viral and Bacterial Acute Respiratory Illness among Older Children and Adults in Rural Western Kenya, 2007-2010

BACKGROUND: Few comprehensive data exist on disease incidence for specific etiologies of acute respiratory illness (ARI) in older children and adults in Africa. METHODOLOGY/PRINCIPAL FINDINGS: From March 1, 2007, to February 28, 2010, among a surveillance population of 21,420 persons >5 years old in rural western Kenya, we collected blood for culture and malaria smears, nasopharyngeal and oropharyngeal swabs for quantitative real-time PCR for ten viruses and three atypical bacteria, and urine for pneumococcal antigen testing on outpatients and inpatients meeting a ARI case definition (cough or difficulty breathing or chest pain and temperature >38.0°C or oxygen saturation <90% or hospitalization). We also collected swabs from asymptomatic controls, from which we calculated pathogen-attributable fractions, adjusting for age, season, and HIV-status, in logistic regression. We calculated incidence by pathogen, adjusting for health-seeking for ARI and pathogen-attributable fractions. Among 3,406 ARI patients >5 years old (adjusted annual incidence 12.0 per 100 person-years), influenza A virus was the most common virus (22% overall; 11% inpatients, 27% outpatients) and Streptococcus pneumoniae was the most common bacteria (16% overall; 23% inpatients, 14% outpatients), yielding annual incidences of 2.6 and 1.7 episodes per 100 person-years, respectively. Influenza A virus, influenza B virus, respiratory syncytial virus (RSV) and human metapneumovirus were more prevalent in swabs among cases (22%, 6%, 8% and 5%, respectively) than controls. Adenovirus, parainfluenza viruses, rhinovirus/enterovirus, parechovirus, and Mycoplasma pneumoniae were not more prevalent among cases than controls. Pneumococcus and non-typhi Salmonella were more prevalent among HIV-infected adults, but prevalence of viruses was similar among HIV-infected and HIV-negative individuals. ARI incidence was highest during peak malaria season. CONCLUSIONS/SIGNFICANCE: Vaccination against influenza and pneumococcus (by potential herd immunity from childhood vaccination or of HIV-infected adults) might prevent much of the substantial ARI incidence among persons >5 years old in similar rural African settings.     

FcgammaRIIA polymorphisms in Streptococcus pneumoniae infection

Invasive pneumococcal disease continues to be a major cause of morbidity and mortality among children and adults worldwide. Effective host defence against Streptococcus pneumoniae depends on immunoglobulin G-mediated phagocytosis of the bacteria and it has been shown in vitro that the FcgammaRIIA polymorphism (FcgammaRIIA-R131 vs FcgammaRIIA-H131) determines the capacity of immunoglobulin G2-mediated phagocytosis via this receptor. In this study, we evaluated FcgammaRIIA polymorphisms in children with pneumococcal sepsis and a number of control groups in order to investigate a possible association of FcgammaRIIA genotypes with Streptococcus pneumoniae infection. The distribution of the genotypes differed in these populations. The frequency of homozygosity for FcgammaRIIA-R/R131 in the patients was significantly higher than that in the healthy random donor population (43%vs 21%, P < 0.05). The frequencies of FcgammaRIIA-H/H131 were similar among all groups of individuals, while the incidence of the heterozygous FcgammaRIIA-R/H131 was lower (35%vs 52%, P < 0.05). Thus, it appears that the FcgammaRIIA-H131 polymorphic form, even in the heterozygous form, may be protective for pneumococcal sepsis and children with FcgammaRIIA-R/R131 genotype could be more at risk of infection with invasive Streptococcus pneu-moniae.     

The synthesis and antibacterial activity of totarol derivatives. Part 2: Modifications at C-12 and O-13

Alterations of the C-12 and C-13 aromatic ring substituents of totarol (1) afforded the series of derivatives 2-14, and introduction of substituents at C-12 gave exclusively 2a-14a. The majority of these analogues were tested in vitro against the following organisms: beta-lactamase-positive and high level gentamycin-resistant Enterococcus faecalis, penicillin-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), and multiresistant Klebsiella pneumoniae. The results were evaluated in terms of structure-activity relationship which reveals that: (a) the phenolic moiety at C-13, in general, is essential for antibacterial activity at < 32 microg/mL against gram-positive species, and (b) derivatization at C-12 has an undesirable effect on the antibacterial activity of this class of compounds, while (c) all compounds tested are ineffective against the gram-negative Klebsiella pneumoniae.     

儿童感染青霉素耐药肺炎链球菌的 多位点序列分型

目的对儿童感染的青霉素耐药肺炎链球菌进行多位点序列分型,了解厦门地区肺炎链球菌青霉素耐药菌株遗传背景。方法采用多位点序列分型法对2012年1月至2014年12月期间分离的60株青霉素耐药肺炎链球菌进行分子分型。结果 60株青霉素耐药肺炎链球菌MLST法共检出24个ST型,其中发现6个新的ST型,分别被命名为ST10004、ST10005、ST10006、ST10007、ST10008和ST10009。存在一个优势型别ST271,占31.7%(19/60),发现了4个克隆群和20种单一克隆,其中主要克隆群为国际流行耐药克隆群Taiwan19F-14,占41.7%(25/60)。结论本地区分离的儿童青霉素耐药肺炎链球菌主要以ST271型为主,属国际流行耐药克隆群Taiwan19F-14,是引起儿童呼吸道感染肺炎链球菌多重耐药的主要原因。     

Upper respiratory tract microbial communities, acute otitis media pathogens, and antibiotic use in healthy and sick children

The composition of the upper respiratory tract microbial community may influence the risk for colonization by the acute otitis media (AOM) pathogens Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. We used culture-independent methods to describe upper respiratory tract microbial communities in healthy children and children with upper respiratory tract infection with and without concurrent AOM. Nasal swabs and data were collected in a cross-sectional study of 240 children between 6 months and 3 years of age. Swabs were cultured for S. pneumoniae, and real-time PCR was used to identify S. pneumoniae, H. influenzae, and M. catarrhalis. The V1-V2 16S rRNA gene regions were sequenced using 454 pyrosequencing. Microbial communities were described using a taxon-based approach. Colonization by S. pneumoniae, H. influenzae, and M. catarrhalis was associated with lower levels of diversity in upper respiratory tract flora. We identified commensal taxa that were negatively associated with colonization by each AOM bacterial pathogen and with AOM. The balance of these relationships differed according to the colonizing AOM pathogen and history of antibiotic use. Children with antibiotic use in the past 6 months and a greater abundance of taxa, including Lactococcus and Propionibacterium, were less likely to have AOM than healthy children (odds ratio [OR], 0.46; 95% confidence interval [CI], 0.25 to 0.85). Children with no antibiotic use in the past 6 months, a low abundance of Streptococcus and Haemophilus, and a high abundance of Corynebacterium and Dolosigranulum were less likely to have AOM (OR, 0.51; 95% CI, 0.31 to 0.83). An increased understanding of polymicrobial interactions will facilitate the development of effective AOM prevention strategies.     

A marked shift in the serotypes of pneumococci isolated from healthy children in Szeged, Hungary, over a 6-year period

Streptococcus pneumoniae is an important pathogen with significant morbidity and mortality rates worldwide, especially among children <5 years. Healthy carriers are the most important sources of pneumococcal infections, and the nasopharyngeal colonisation is the most prevalent among children attending communities such as day-care centres (DCCs). The conjugate pneumococcal vaccines (PCVs) were shown to have an impact on the colonisation, and so play an important role in inhibiting infections. In this study we compared the nasal carriage of healthy children attending DCCs in Szeged, Hungary in 2003/2004, when nobody was vaccinated, and in 2010, when already 1/5 of the children received PCV-7. Significant differences were observed in the serotype distribution, representing a marked shift from the previously widespread vaccine-types (mostly 6A or 14) to others (11A and 23F). The new serotypes showed higher antibiotic susceptibility. The bacterium exchange between children was clear from the pulsed-field gel electrophoresis (PFGE) patterns, and the circulation of certain international clones plays also a role in these dynamic changes.     

677例新生儿咽拭子细菌培养及病原菌的耐药性分析

为观察首都医科大学附属北京妇产医院新生儿重症监护室(neonatal intensive care unit,NICU)患儿主要定植细菌及其抗生素耐药情况,以便采取相应措施及时控制医院内感染,本研究选择2014年8月1日-2015年5月31日住院患儿的咽试子标本进行细菌培养,同时进行耐药性分析。677例新生儿咽拭子培养结果显示,230例阳性(34.0%),其中革兰阳性球菌159例(69.1%),革兰阴性杆菌71例(30.9%)。定植细菌中,革兰阳性球菌主要为草绿色链球菌、克氏库克菌及表皮葡萄球菌,革兰阴性杆菌主要为大肠埃希菌、鲍曼不动杆菌及肺炎克雷伯菌。各细菌对常用抗生素的耐药率不同,同时进行药敏试验有助于指导临床用药。     

Bacterial etiology of otitis media with effusion; focusing on the high positivity of Alloiococcus otitidis

The etiology of otitis media with effusion (OME) is unclear. The bacterial analyses of middle ear effusion (MEE) in OME may reveal important information regarding its etiology. Alloiococcus otitidis, Heamophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis were investigated by using microbiologic culture and a multiplex PCR method in the middle ear fluid of 32 children (54 samples) with chronic OME. PCR yielded positive results in 18 (33.3%) middle ear effusions while culture resulted positive for 3 (5.6%). The PCR method detected A. otitidis in 10 (18.5%) specimens, H. influenzae in 7 (13%), M. catarrhalis in 4 (7.4%) and S. pneumoniae in 2 (3.7%) specimens. The multiplex PCR method enhances the detection rate significantly compared to that of the conventional culture method. A. otitidis is the most common detected pathogen in the MEE of the OME.     

The role of anaerobic bacteria in acute and chronic mastoiditis

Mastoiditis (M) is the most common intratemporal complication of otitis media. The incidence of M has decreased since the advent of antimicrobial agents. In the last decade, however, there has been a marked increased in the incidence of acute M in several communities, sometimes in association with the growing resistance of pneumococci. Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus and Haemophillus influenzae are the most common organisms recovered in acute M. Several recent studies demonstrated the predominance of Pseudomonas aeruginosa in this infection. However, because P. aeruginosa colonizes the ear canal it can contaminate specimens obtained through the non-sterile ear canal. P. aeruginosa, Enterobacteriaceae, S. aureus and anaerobic bacteria are the most common isolates in chronic M. Anaerobes predominate in studies where adequate methods for their isolation are employed. Management of uncomplicated M requires the administration of parenteral antimicrobial therapy and myringotomy with or without tympanostomy tube placement. If no improvement occurs within 48 h, surgical intervention and drainage may be necessary. The procedure generally employed is simple mastoidectomy, and tympanostomy tube placement. Radical mastoidectomy is performed only if there is no improvement after simple mastoidectomy.