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Macrolide susceptibility and serotype specific macrolide resistance of invasive isolates of Streptococcus pneumoniae in Germany from 1992 to 2008
Matthias Im?hl, Ralf Reinert, Christina Mutscher, Mark van der Linden
BMC Microbiology , 2010, DOI: 10.1186/1471-2180-10-299
Abstract: From 1992 to 2008, data on macrolide susceptibility were available for 11,807 invasive isolates. 8,834 isolates (74.8%) were from adults (≥ 16 years), and 2,973 isolates (25.2%) from children (< 16 years). The overall nonsusceptibility rate of all isolates was 16.2% (intermediate, 0.2%; resistant, 16.0%). Higher resistance rates were observed among children (intermediate, 0.2%; resistant, 23.8%) than among adults (intermediate, 0.3%; resistant 13.4%). Maximum nonsusceptibility rates during the period under study were observed in 2005 (children: intermediate, 0.3%; resistant, 32.3%; adults: intermediate, 0.0%; resistant, 18.6%), while nonsusceptibility rates in 2008 were considerably lower, especially for children (children: intermediate, 0.0%; resistant, 15.2%; adults: intermediate, 0.1%; resistant, 12.9%). The rate of resistance was higher among the vaccine serotypes (7-valent, 36.6%; 10-valent, 28.2%; 13-valent, 24.3%) than among the non vaccine serotypes (non 7-valent, 6.5%; non 10-valent, 7.4%; non 13-valent, 6.3%). Serotype 14 (69.6% nonsusceptibility) proved to be the most resistant serotype.There has been a considerable and statistically significant decrease in macrolide nonsusceptibility in Germany since 2005, especially among children.Streptococcus pneumoniae is a leading pathogen in bacterial pneumonia, sepsis and meningitis in humans worldwide [1,2]. In many European countries the rate of resistance of S. pneumoniae to macrolides has exceeded that of penicillin [3]. Concerning penicillin, it has been described that treatment of patients with nonmeningeal invasive pneumococcal infections with nonsusceptible isolates was not associated with higher mortality rates [4-6]. In 2008 new penicillin breakpoints for S. pneumoniae were published by the CLSI [7], differentiating meningitis and non-meningitis cases of invasive pneumococcal disease (IPD). Their impact on susceptibility categorisation in Germany was described previously by our group [8]. However, for ma
Macrolide-resistant phenotypes of invasive streptococcus pneumoniae isolates in Serbia
Gaji? Ina,Opavski Nata?a,Mija? Vera,Ranin L.
Archives of Biological Sciences , 2012, DOI: 10.2298/abs1204377g
Abstract: Macrolide resistance in Streptococcus pneumoniae has emerged as an important worldwide problem over the past decade. The aim of this study was to investigate macrolide-resistant phenotypes and the antimicrobial susceptibility patterns of invasive pneumococci in Serbia. A total of 68 invasive pneumococcal strains, collected from 2009 to 2011, were sent from regional laboratories to the National Reference Laboratory. Susceptibility testing was performed using the VITEK2 system and phenotypes were determined by triple-test. Overall penicillin and erythromycin nonsusceptibility rates were 26% and 43%, respectively. Resistance rates were higher in children than in adults. Co-resistance to penicillin and erythromycin was detected in 18% strains. Resistance rates to the third generation of cephalosporins, TMP-SXT and tetracycline were 16%, 37% and 29%, respectively. All isolates were fully susceptible to vancomycin, linezolid, fluoroquinolones, telithromycin and rifampicin. Twenty-two isolates (79%) an expressed macrolide-lincosamide-streptogramin B (MLSB) resistance phenotype and M phenotype was found in 21% of macrolide resistant strains. [Projekat Ministarstva nauke Republike Srbije, br. 175039]
Serotype-specific mortality from invasive Streptococcus pneumoniae disease revisited
Pernille Martens, Signe Worm, Bettina Lundgren, Helle Konradsen, Thomas Benfield
BMC Infectious Diseases , 2004, DOI: 10.1186/1471-2334-4-21
Abstract: Retrospective review of 464 cases of invasive disease among adults diagnosed between 1990 and 2001. Multivariate Cox proportional hazard analysis.After adjustment for other markers of disease severity, we found that infection with serotype 3 was associated with an increased relative risk (RR) of death of 2.54 (95% confidence interval (CI): 1.22–5.27), whereas infection with serotype 1 was associated with a decreased risk of death (RR 0.23 (95% CI, 0.06–0.97)). Additionally, older age, relative leucopenia and relative hypothermia were independent predictors of mortality.Our study shows that capsular serotypes independently influenced the outcome from invasive pneumococcal disease. The limitations of the current polysaccharide pneumococcal vaccine warrant the development of alternative vaccines. We suggest that the virulence of pneumococcal serotypes should be considered in the design of novel vaccines.Streptococcus pneumoniae (pneumococci) is a leading cause of pneumonia, sepsis, and meningitis among adults. Mortality associated with invasive disease remains high at 5–35% depending on site of infection, age and comorbidity [1-4].Ninety different capsular serotypes cause disease among humans but less than 30 types account for the majority (>90%) of invasive cases [5]. The capsular polysaccharide plays an important role in pneumococcal pathogenesis, e.g. its diversity allowed for immune evasion by preventing phagocytosis in non-immune individuals [6], the amount of capsular polysaccharide correlated with pneumococcal virulence [7,8], during experimental pneumococal meningitis serotypes 3, 6B, 14, 23F caused more severe meningeal inflammation than serotypes 1, 5, 9 and 7F [9,10]. and in a murine model of pneumococcal sepsis certain serotypes were more lethal than others [11]. In adult case series, unadjusted mortality rates from invasive disease were increased with serotypes 3 and 5 while infection with serotypes 1, 4, 9V 12F and 14 were associated with lower mortality
Serotype and Genotype Distribution among Invasive Streptococcus pneumoniae Isolates in Colombia, 2005–2010  [PDF]
Eliana L. Parra, Viviana Ramos, Olga Sanabria, Jaime Moreno
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0084993
Abstract: In Colombia, a laboratory-based surveillance of invasive Streptococcus pneumoniae isolates as part of SIREVA II PAHO has been conducted since 1994. This study describes the serotype distribution, antimicrobial resistance, and genetic relationships of pneumococcal isolates recovered in Colombia from 2005 to 2010. In this study, demographic data of invasive S. pneumoniae isolates were analyzed, and antimicrobial susceptibility patterns were determined. Pulse field gel electrophoresis (n = 629) and multilocus sequence typing (n = 10) were used to determine genetic relationship of isolates with minimal inhibitory concentration to penicillin ≥0.125 μg/mL. A total of 1775 isolates of S. pneumoniae were obtained. Fifteen serotypes accounted for 80.7% of isolates. Serotype 14 (23.1%) was the most frequent in the general population. Penicillin resistance was 30.7% in meningitis and 9.0% in non-meningitis. Clones Spain6BST90, Spain9VST156, Spain23FST81, and Colombia23FST338 were associated to isolates. Additionally, serotype 6A isolates were associated with ST460 and ST473, and 19A isolates with ST276, ST320, and ST1118. In conclusion, the surveillance program provided updated information of trends in serotype distribution, antimicrobial resistance and the circulation of clones in invasive pneumococcal diseases. These results could be helpful to understand the epidemiology of S. pneumoniae in Colombia, and provide a baseline to measure the impact of vaccine introduction.
Serotype Distribution and Antimicrobial Resistance of Streptococcus pneumoniae Isolates Causing Invasive Diseases from Shenzhen Children’s Hospital  [PDF]
Xiang Ma, Ruizhen Zhao, Zhuoya Ma, Kaihu Yao, Sangjie Yu, Yuejie Zheng, Yonghong Yang
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0067507
Abstract: Objective To provide guidance for clinical disease prevention and treatment, this study examined the epidemiology, antibiotic susceptibility, and serotype distribution of Streptococcus pneumoniae (S. pneumoniae) associated with invasive pneumococcal diseases (IPDs) among children less than 14 years of age in Shenzhen, China. Materials and Methods All the clinical strains were isolated from children less than 14 years old from January 2009 to August 2012. The serotypes and antibiotic resistance of strains of S. pneumoniae were determined using the capsular swelling method and the E-test. Results A total of 89 strains were isolated and 87 isolates were included. The five prevailing serotypes were 19F (28.7%), 14 (16.1%), 23F (11.5%), 19A (9.2%) and 6B (6.9%). The most common sequence types (ST) were ST271 (21.8%), ST876 (18.4%), ST320 (8.0%) and ST81 (6.9%) which were mainly related to 19F, 14, 19A and 23F, respectively. The potential coverage by 7-, 10-, and 13-valent pneumococcal conjugate vaccine were 77.0%, 77.0%, and 89.7%, respectively. Among the 87 isolates investigated, 11.5% were resistant to penicillin, and for meningitis isolates, the resistance rate was 100%. Multi-drug resistance (MDR) was exhibited by 49 (56.3%) isolates. Eighty-four isolates were resistance to erythromycin, among which, 56 (66.7%) carried the ermB gene alone and 28 (33.3%) expressed both the ermB and mefA/E genes. Conclusions The potential coverage of PCV13 is higher than PCV7 and PCV10 because high rates of serotypes 19A and 6A in Shenzhen. The clinical treatment of IPD needs a higher drug concentration of antibiotics. Continued surveillance of the antimicrobial susceptibility and serotypes distribution of IPD isolates may be necessary.
Invasive isolates of Streptococcus pneumoniae in Serbia: Antimicrobial susceptibility and serotypes  [PDF]
Gaji? Ina,Mija? Vera,Ranin Lazar,An?elkovi? Dragana
Srpski Arhiv za Celokupno Lekarstvo , 2013, DOI: 10.2298/sarh1302048g
Abstract: Introduction. Streptococcus pneumoniae is one of the leading causes of bacterial meningitis and sepsis. Invasive pneumococcal disease is a significant medical problem worldwide, particularly in children, due to a huge increase of pneumococcal resistance to antibiotics. Objective. The aim of the study was to investigate the antimicrobial susceptibility pattern of invasive pneumococcal isolates, as well as to determine whether decreased S. pneumoniae susceptibility to antibiotics was related to a particular serotype. Methods. Antimicrobial susceptibility to 19 antibiotics was determined in 58 invasive pneumococcal strains that were collected from seven regional centers during the period July 2009 to February 2011 in the National Reference Laboratory for streptococci and pneumococci. Results. The overall nonsusceptibility rate to penicillin was detected in 34% of pneumococcal isolates and to erythromycin in 36%. Higher resistance rates were observed among children than among adults. Penicillin resistance rate was 65% in children versus 22% in adults, while erythromycin nonsusceptibility rate was 47% in children versus 32% in adults. Co-resistance to penicillin and erythromycin was detected in 21% strains, mostly isolated from children. Multiresistance was found in one third of isolates. All strains were susceptible to vancomycin, linezolid, fluoroquinolones, telithromycin and rifampicin, while 23 (40%) isolates were susceptible to all tested antibiotics. The most common resistant serotypes were 19F and 14. Conclusion. The study has revealed that penicillin and macrolide resistance among invasive pneumococcal isolates is very high in Serbia. This emphasizes the need for continuous monitoring for invasive pneumococcal disease to document the serotype distribution and antimicrobial susceptibility pattern. [Projekat Ministarstva nauke Republike Srbije, br. 175039: Bakterije rezistentne na antibiotike u Srbiji - fenotipska i genotipska karakterizacija]
Complete genome sequence of a serotype 11A, ST62 Streptococcus pneumoniae invasive isolate
Romina Camilli, Raoul JP Bonnal, Maria Del Grosso, Michele Iacono, Giorgio Corti, Ermanno Rizzi, Magda Marchetti, Laura Mulas, Francesco Iannelli, Fabiana Superti, Marco R Oggioni, Gianluca De Bellis, Annalisa Pantosti
BMC Microbiology , 2011, DOI: 10.1186/1471-2180-11-25
Abstract: The genome sequence of S. pneumoniae AP200 is 2,130,580 base pair in length. The genome carries 2216 coding sequences (CDS), 56 tRNA, and 12 rRNA genes. Of the CDSs, 72.9% have a predicted biological known function. AP200 contains the pilus islet 2 and, although its phenotype corresponds to serotype 11A, it contains an 11D capsular locus. Chromosomal rearrangements resulting from a large inversion across the replication axis, and horizontal gene transfer events were observed. The chromosomal inversion is likely implicated in the rebalance of the chromosomal architecture affected by the insertions of two large exogenous elements, the erm(TR)-carrying Tn1806 and a functional prophage designated ?Spn_200. Tn1806 is 52,457 bp in size and comprises 49 ORFs. Comparative analysis of Tn1806 revealed the presence of a similar genetic element or part of it in related species such as Streptococcus pyogenes and also in the anaerobic species Finegoldia magna, Anaerococcus prevotii and Clostridium difficile. The genome of ?Spn_200 is 35,989 bp in size and is organized in 47 ORFs grouped into five functional modules. Prophages similar to ?Spn_200 were found in pneumococci and in other streptococcal species, showing a high degree of exchange of functional modules. ?Spn_200 viral particles have morphologic characteristics typical of the Siphoviridae family and are capable of infecting a pneumococcal recipient strain.The sequence of S. pneumoniae AP200 chromosome revealed a dynamic genome, characterized by chromosomal rearrangements and horizontal gene transfers. The overall diversity of AP200 is driven mainly by the presence of the exogenous elements Tn1806 and ?Spn_200 that show large gene exchanges with other genetic elements of different bacterial species. These genetic elements likely provide AP200 with additional genes, such as those conferring antibiotic-resistance, promoting its adaptation to the environment.Streptococcus pneumoniae is a Gram-positive human pathogen responsib
Distribución de serotipos de Streptococcus pneumoniae aislados de infecciones invasoras en el Hospital de Ni os de Santa Fe Serotype distribution of Streptococcus pneumoniae isolated from invasive infections at the Hospital de Ni os of Santa Fe.  [cached]
C. Mayoral,M. R. Baroni,R. Giani,S. Virgolini
Revista argentina de microbiolog?-a , 2008,
Abstract: Con la introducción de vacunas conjugadas antineumocócicas se observó, en muchos países, disminución de aislamientos de Streptococcus pneumoniae del serotipo 14 y aumento de aislamientos correspondientes a serotipos no incluidos en esas vacunas. En 1993, el Hospital de Ni os de Santa Fe comenzó la vigilancia de la distribución de serotipos de Streptococcus pneumoniae invasores. En este trabajo se estudió la correlación entre serotipo y a) patología (neumonía/meningitis), b) edad (menor o mayor de dos a os), y c) CIM de penicilina, para los serotipos aislados en el período 2003-2005. El serotipo predominante fue el 14, seguido del 1, 6B, 18C, 7F, 19F y 5. El serotipo 14 mostró asociación estadísticamente significativa con valores de CIM de penicilina entre 0,5 y 2 mg/l, no así con alguna patología, aunque se lo halló con mayor frecuencia en neumonías que en meningitis. Los serotipos 14 y 1 prevalecieron en ni os menores y mayores de 2 a os, respectivamente. La CIM de penicilina = 2 mg/l se observó más en neumonías que en meningitis. La frecuencia relativa de los diferentes serotipos hallados fue semejante a la observada en el período 1993-99; no obstante, los serotipos 18C, 4, 12F y 22F no se habían encontrado antes. La aparición de nuevos serotipos convierte en importante la vigilancia, dada la necesidad de formular vacunas que los incluyan y que efectivamente prevengan las infecciones neumocócicas más comunes. The serotype distribution of Streptococcus pneumoniae varies through time. The introduction of pneumococcal conjugate vaccines showed a decreased prevalence of pneumococcal invasive isolates belonging to serotype 14 and an increase of serotypes not therein included. In 1993, the Hospital de Ni os of Santa Fe began surveillance of the serotype distribution of invasive S. pneumoniae disease. In the period 2003 - 2005, 76 isolates were analysed by studying the correlation between serotype and pathology, age and MIC of penicillin. Serotype 14 was the most frequent followed by serotypes 1, 6B, 18C, 7F, 19 F and 5. Serotype 14 showed a statistically significant correlation with MICs of penicillin ranging from 0,5 to 2 mg/l. Although this serotype was more frequently observed in pneumonia than in meningitis, there was not a significant association with any particular pathology. Serotypes 14 and 1, were prevalent among children under and over 2 years old, respectively. Most of these isolates with MICs of penicillin = 2 mg/l, were from patients with pneumonia and not with meningitis. The serotype distribution was similar to that during the period 1993-99,
Macrolide resistance determinants among Streptococcus pneumoniae isolates from carriers in Central Greece  [cached]
Grivea Ioanna N,Sourla Alexia,Ntokou Eleni,Chryssanthopoulou Denise C
BMC Infectious Diseases , 2012, DOI: 10.1186/1471-2334-12-255
Abstract: Background We sought to characterize the temporal trends in nasopharyngeal carriage of macrolide-resistant pneumococci during a period with increased heptavalent pneumococcal conjugate vaccine (PCV7) coverage in Central Greece. Methods Streptococcus pneumoniae isolates were recovered from 2649 nasopharyngeal samples obtained from day-care center attendees in Central Greece during 2005–2009. A phenotypic and genotypic analysis of the isolates was performed, including the identification of macrolide resistance genes mef(A), subclasses mef(A) and mef(E), as well as erm(B). Results Of the 1105 typeable S. pneumoniae isolates, 265 (24%) were macrolide-resistant; 22% in 2005, 33.3% in 2006, 23.7% in 2007, and 20.5% in 2009 (P=0.398). Among these macrolide-resistant pneumococci, 28.5% possessed erm(B), 24.3% erm(B)+mef(E), 41.8% mef(E), and 5.3% mef(A). A mef gene as the sole resistance determinant was carried by 31% of macrolide-resistant isolates belonging to PCV7 serotypes and 75.8% of the non-PCV7 serotypes. Across the 4 annual surveillances, pneumococci carrying mef(A) gradually disappeared, whereas serotype 19F isolates carrying both erm(B) and mef(E) persisted without significant yearly fluctuations. Among isolates belonging to non-PCV7 serotypes, macrolide-resistance was observed in those of serotypes 6A, 19A, 10A, 15A, 15B/C, 35F, 35A, and 24F. In 2009, ie 5 years after the introduction of PCV7 in our country, 59% of macrolide-resistant pneumococci belonged to non-PCV7 serotypes. Conclusions Across the study period, the annual frequency of macrolide-resistant isolates did not change significantly, but in 2009 a marked shift to non-PCV7 serotypes occurred. Overall, more than half of the macrolide-resistant isolates possessed erm(B) either alone or in combination with mef(E). erm(B) dominated among isolates belonging to PCV7 serotypes, but not among those of non-PCV7 serotypes.
Fatal meningitis in a previously healthy young adult caused by Streptococcus pneumoniae serotype 38: an emerging serotype?
Carolyn I Baker, Christopher P Barrozo, Margaret AK Ryan, Lisa A Pearse, Kevin L Russell
BMC Infectious Diseases , 2005, DOI: 10.1186/1471-2334-5-38
Abstract: Traditional and molecular methods were utilized to determine the serotype of the infecting pneumococcus. The pneumococcal isolate was identified as serotype 38 (PS38), a serotype not covered by current vaccine formulations. The global significance of this serotype was explored in the medical literature, and found to be a rare but recognized cause of carriage and invasive disease.The potential of PS38 to cause severe disease is documented in this report. Current literature does not support the hypothesis that this serotype is increasing in incidence. However, as we monitor the changing epidemiology of pneumococcal illness in the US in this conjugate era, PS38 might find a more prominent and concerning niche as a replacement serotype.In December 2001, the Department of Defense Center for Deployment Health Research at the Naval Health Research Center (NHRC) was consulted regarding a case of fatal meningitis caused by Streptococcus pneumoniae (pneumococcus) in a Marine Corps recruit.The pneumococcus is a common cause of fatal bacterial meningitis in the US [1]. A 23-valent polysaccharide vaccine and a 7-valent conjugate pneumococcal vaccine are available and potentially effective in protecting against serotype-specific invasive infections. For this reason, it is important to determine whether clinically significant pneumococcal infections are vaccine-covered serotypes, particularly in settings like military training camps where epidemic spread can occur.On December 22, 2001, an 18-year-old male in his eighth week of Marine Corps basic training presented to the field medical station with headache and an episode of vomiting after physical training.His neurological symptoms progressed over the next several hours until he became disoriented and unresponsive. He was evaluated in the local hospital emergency department where a fever of 39.1C (102.5F) and disorientation to person, place, and time were observed. Lumbar puncture performed during medical evaluation revealed an op
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