Penicillin-nonsusceptible Streptococcus Pneumoniae Research Articles

Integrated genomic analysis of antibiotic resistance and virulence determinants in invasive strains of Streptococcus pneumoniae

IntroductionStreptococcus pneumoniae is an important human pathogen that may cause severe invasive pneumococcal diseases (IPDs) in young children and the elderly. A comprehensive comparative whole-genome analysis of invasive and non-invasive serotype strains offers great insights that are applicable to vaccine development and disease control.MethodsIn this study, 58 invasive (strains isolated from sterile sites) and 71 non-invasive (serotypes that have not been identified as invasive in our study) pneumococcal isolates were identified among the 756 pneumococcal isolates obtained from seven hospitals in Zhejiang, China (2010–2022). Serotyping, antimicrobial resistance tests, and genomic analyses were conducted to characterize these strains.Results and discussionThe three most invasive serotypes were 23F, 14, and 6B. The invasive pneumococcal isolates' respective resistance rates against penicillin, ceftriaxone, tetracycline, and erythromycin were 34.5%, 15.5%, 98.3%, and 94.7%. Whole-genome sequencing indicated that the predominant invasive clonal complexes were CC271, CC876, and CC81. The high rate of penicillin non-susceptible Streptococcus pneumoniae (PNSP) is related to the clonal distribution of resistance-conferring penicillin-binding proteins (PBP). Interestingly, we found a negative correlation between invasiveness and resistance in the invasive pneumococcal serotype strains, which might be due to the proclivity of certain serotypes to retain their β-lactam resistance. Moreover, the mutually exclusive nature of zmpC and rrgC+srtBCD suggests their intricate and potentially redundant roles in promoting the development of IPD. These findings reveal significant implications for pneumococcal vaccine development in China, potentially informing treatment strategies and measures to mitigate disease transmission.

Penicillin-binding protein genotyping of penicillin-nonsusceptible Streptococcus pneumoniae isolates from the nasopharynx of healthy preschool children

Abstract Streptococcus pneumoniae is one of the most frequent bacterial identified causes of community-acquired pneumonia, otitis media and meningitis. It is, as well, a common cause of bacteraemia’s significant morbidity and mortality. Beta-lactam antibiotics (BLAs) are the first line of empirical treatment for pneumococcal infections. The targets of BLAs are penicillin-binding proteins (PBPs), the modifications of which are one of the reasons why pneumococci are non-susceptible to BLAs. In our work, a total of 39 Streptococcus pneumoniae isolates were obtained from 176 healthy children, both vaccinated and non-vaccinated. The isolates were tested for antimicrobial susceptibility, and their penicillin-binding proteins (PBPs) were typed by the restriction fragment length of the polymorphism analysis of their pbp genes. The most frequent serotypes among the penicillin non-susceptible Streptococcus pneumoniae (PNSSP) isolates were 23B, 35B and 19F. Restriction enzyme analyses of pbp1a, pbp2b, and pbp2x genes revealed 5, 3 and 3 different patterns, respectively, and a total of 4 different PBPs profiles of PNSSP isolates belonging to serotypes not included in pneumococcal conjugate vaccines were demonstrated. We conclude that the level of resistance should be monitored constantly to ascertain the effect of current pneumococcal conjugate vaccines, as well as to recognize new circumstances developing in Poland, as well as the possibility of multiple, independent imports of resistant strains from abroad.

Genetic determinants of macrolide and tetracycline resistance in penicillin non-susceptible Streptococcus pneumoniae isolates from people living with HIV in Dar es Salaam, Tanzania

BackgroundOver one million yearly deaths are attributable to Streptococcus pneumoniae and people living with HIV are particularly vulnerable. Emerging penicillin non-susceptible Streptococcus pneumoniae (PNSP) challenges therapy of pneumococcal disease. The aim of this study was to determine the mechanisms of antibiotic resistance among PNSP isolates by next generation sequencing.MethodsWe assessed 26 PNSP isolates obtained from the nasopharynx from 537 healthy human immunodeficiency virus (HIV) infected adults in Dar es Salaam, Tanzania, participating in the randomized clinical trial CoTrimResist (ClinicalTrials.gov identifier: NCT03087890, registered on 23rd March, 2017). Next generation whole genome sequencing on the Illumina platform was used to identify mechanisms of resistance to antibiotics among PNSP.ResultsFifty percent (13/26) of PNSP were resistant to erythromycin, of these 54% (7/13) and 46% (6/13) had MLSB phenotype and M phenotype respectively. All erythromycin resistant PNSP carried macrolide resistance genes; six isolates had mef(A)-msr(D), five isolates had both erm(B) and mef(A)-msr(D) while two isolates carried erm(B) alone. Isolates harboring the erm(B) gene had increased MIC (> 256 µg/mL) towards macrolides, compared to isolates without erm(B) gene (MIC 4-12 µg/mL) p < 0.001. Using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines, the prevalence of azithromycin resistance was overestimated compared to genetic correlates. Tetracycline resistance was detected in 13/26 (50%) of PNSP and all the 13 isolates harbored the tet(M) gene. All isolates carrying the tet(M) gene and 11/13 isolates with macrolide resistance genes were associated with the mobile genetic element Tn6009 transposon family. Of 26 PNSP isolates, serotype 3 was the most common (6/26), and sequence type ST271 accounted for 15% (4/26). Serotypes 3 and 19 displayed high-level macrolide resistance and frequently carried both macrolide and tetracycline resistance genes.ConclusionThe erm(B) and mef(A)-msr(D) were common genes conferring resistance to MLSB in PNSP. Resistance to tetracycline was conferred by the tet(M) gene. Resistance genes were associated with the Tn6009 transposon.

Serotype Distribution, Antimicrobial Susceptibility, Multilocus Sequencing Type and Virulence of Invasive Streptococcus pneumoniae in China: A Six-Year Multicenter Study.

Background: Streptococcus pneumoniae is an important human pathogen that can cause severe invasive pneumococcal diseases (IPDs). The aim of this multicenter study was to investigate the serotype and sequence type (ST) distribution, antimicrobial susceptibility, and virulence of S. pneumoniae strains causing IPD in China.Methods: A total of 300 invasive S. pneumoniae isolates were included in this study. The serotype, ST, and antimicrobial susceptibility of the strains, were determined by the Quellung reaction, multi-locus sequence typing (MLST) and broth microdilution method, respectively. The virulence level of the strains in the most prevalent serotypes was evaluated by a mouse sepsis model, and the expression level of well-known virulence genes was measured by RT-PCR.Results: The most common serotypes in this study were 23F, 19A, 19F, 3, and 14. The serotype coverages of PCV7, PCV10, PCV13, and PPV23 vaccines on the strain collection were 42.3, 45.3, 73.3 and 79.3%, respectively. The most common STs were ST320, ST81, ST271, ST876, and ST3173. All strains were susceptible to ertapenem, levofloxacin, moxifloxacin, linezolid, and vancomycin, but a very high proportion (>95%) was resistant to macrolides and clindamycin. Based on the oral, meningitis and non-meningitis breakpoints, penicillin non-susceptible Streptococcus pneumoniae (PNSP) accounted for 67.7, 67.7 and 4.3% of the isolates, respectively. Serotype 3 strains were characterized by high virulence levels and low antimicrobial-resistance rates, while strains of serotypes 23F, 19F, 19A, and 14, exhibited low virulence and high resistance rates to antibiotics. Capsular polysaccharide and non-capsular virulence factors were collectively responsible for the virulence diversity of S. pneumoniae strains.Conclusion: Our study provides a comprehensive insight into the epidemiology and virulence diversity of S. pneumoniae strains causing IPD in China.

Is Penicillin-Nonsusceptible Streptococcus pneumoniae a Significant Challenge to Healthcare System? A Systematic Review and Meta-Analysis.

Background In recent years, antibiotic-resistant pathogens including penicillin-nonsusceptible Streptococcus pneumoniae (PNSP) have posed serious threats against human health. The aim of this meta-analysis was to investigate the prevalence of Streptococcus pneumoniae drug resistance particularly the incidence of PNSP strains in Iran. Methods A systematic search was done in national and international electronic databases using Persian and English keywords. Up until May 20, 2020, a total of 58 publications were detected as eligible articles based on the inclusion and exclusion criteria, and then the selected studies were enrolled for data extraction and meta-analysis according to the PRISMA guidelines. Results A high rate of PNSP (46.9%) and multidrug-resistant (MDR) S. pneumoniae (45.3%) in our isolates were evident. Furthermore, total frequency resistance to other drugs in S. pneumoniae was as follows: erythromycin 41.1%, azithromycin 53.2%, tetracycline 39.9%, levofloxacin 1.7%, rifampin 1.2%, clindamycin 31.7%, vancomycin 1.7%, trimethoprim/sulfamethoxazole 63.9%, chloramphenicol 20%, ceftriaxone 10.9%, amoxicillin 30.5%, ciprofloxacin 8.3%, imipenem 6.1%, linezolid 0%, and cefotaxime 8.3%. Conclusion Although the overall prevalence of cephalosporin- and carbapenem-resistant Streptococcus pneumoniae was low, penicillin-resistant strains, especially PNSP, could become a significant challenge to the healthcare system in Iran. Hence, the prescription of penicillin as the first-choice antibiotic in the treatment of S. pneumoniae infections should be avoided.

Genomic epidemiology of penicillin-non-susceptible Streptococcus pneumoniae.

Penicillin-non-susceptible Streptococcus pneumoniae (PNSP) were first detected in the 1960s, and are now common worldwide, predominantly through the international spread of a limited number of strains. Extant PNSP are characterized by mosaic pbp2x, pbp2b and pbp1a genes generated by interspecies recombinations, with the extent of these alterations determining the range and concentrations of β-lactams to which the genotype is non-susceptible. The complexity of the genetics underlying these phenotypes has been the subject of both molecular microbiology and genome-wide association and epistasis analyses. Such studies can aid our understanding of PNSP evolution and help improve the already highly-performing bioinformatic methods capable of identifying PNSP from genomic surveillance data.

Molecular serotyping and genotyping of penicillin non-susceptible pneumococci: the introduction of new sequence types, Tehran, Iran.

The emergence of penicillin non-susceptible Streptococcus pneumoniae (PNSP) isolates can pose significant challenges to today's health-care system. Resistant clonal isolates are disseminated in different regions and countries, and this study was focused on the description of the epidemiological spread of these strains. Clinical samples were collected from individuals admitted to hospitals affiliated to the Tehran University of Medical Sciences, Iran. To investigate the molecular characteristics of PNSP isolates, they were subjected to molecular typing using multi-locus sequence typing (MLST). Serotype distributions of S. pneumoniae isolates were also evaluated by multiplex PCR assay. The most prevalent serotypes in the PNSP isolates were 23F, 19F, 14, 3 and 9V. Two isolates were considered as a non-vaccine serotype. The MLST analysis showed that PNSP isolates belonged to five different clonal complexes (CC180, CC217, CC81, CC63 and CC320) and 42% (5/12) of the sequence types were novel (12936, 12937, 12938, 12939 and 12940). This study indicates the high level of heterogeneity that is present among PNSP isolates. Unexpected high genetic diversity in small populations indicates consecutive diversification of resistant strains.

Linezolid activity against clinical Gram-positive cocci with advanced antimicrobial drug resistance in Iran.

The aim of the study was to investigate the linezolid activity against clinical Gram-positive cocci with advanced antimicrobial drug resistance. A collection of methicillin resistant Staphylococcus aureus (MRSA), vancomycin resistant enterococci (VRE), penicillin non-susceptible Streptococcus pneumoniae (PNSP), and group B streptococci (GBS) were isolated from various clinical samples. Antimicrobial susceptibility tests were done using standard methods Subsequently, we investigated linezolid antibacterial activities, the first approved oxazolidinone against isolates by the standard broth microdilution method. According to our results, MRSA and PNSP isolates were multidrug resistant, and almost half of the VRE isolates were high level gentamicin resistant (HLGR). Furthermore, resistance to linezolid was not seen among the isolates. The MIC90 values for MRSA, VRE, PNSP and GBS isolates were 4μg/ml, 2μg/ml, 1μg/ml, and 0.5μg/ml, respectively. Only 6.25% of vancomycin resistant enterococci showed intermediate susceptibility to this antibiotic. These findings indicate that linezolid has an excellent activity against clinical drug resistant Gram-positive isolates in Iran. Constant monitoring and surveillance of linezolid MIC distribution allows the researchers to assess and detect gradual upward MIC drifts.

Temporal trends and clonal diversity of penicillin non-susceptible pneumococci from meningitis cases from 1996 to 2012, in Salvador, Brazil.

BackgroundHospital-based surveillance for pneumococcal meningitis has been conducted since January 1996 in the city of Salvador, Brazil. The purpose of this study was to describe the temporal evolution of Penicillin Non-Susceptible Streptococcus pneumoniae (PNSSP) in regards to serotype distributions and clonal diversity recovered from meningitis cases over 17 years.MethodsBroth microdilution was used to identify pneumococcal isolates that were PNSSP (Minimum Inhibitory Concentration > 0.12 μg/ml). The annual incidence rate of meningitis cases was calculated. Serotyping was defined using multiplex polymerase chain reaction assays and quellung reaction. Genetic diversity of PNSSP isolates was assessed using both pulsed-field gel electrophoresis (PFGE) and Multilocus Sequence Typing (MLST) analyses.ResultsA total of 854cerebrospinal fluid (CSF) culture pneumococcal isolates were tested by broth microdilution method and serotyped. A total of 173 (20.3 %) were penicillin non-susceptible (PNSSP) (Minimum Inhibitory concentration ≥ 0.12 μg/ml). The annual incidence of meningitis cases declined from 1.65/100,000 population (1996) to 0.2/100,000 population in 2012 and the rate due to PNSSP declined 82 % over the 17-years of surveillance. PNSSP isolates were restricted to 13 serotypes, being the most common ones serotypes14 (45.1 %; 78/173), 23 F (19.1 %; 33/173), 6B (14.4 %; 25/173), 19 F (9.2 %; 16/173) and 19A (5.2 %; 9/173). Among the PNSSP isolates, 94 % had serotypes represented in the 10-valent conjugate vaccine (PCV10). The predominant serotype 14 clonal groups were identified as PFGE group A/multilocus sequence type 66 (ST66) [35.3 % (61/173)] and PFGE group GK/ST156 [4.6 % (8/173)], the latter one associated with high level resistance to penicillin and ceftriaxone.ConclusionsOur results show sustained reductions in pneumococcal meningitis cases in the Metropolitan region of Salvador from 1996 to 2012. This might reflect a beneficial impact of conjugate vaccines. Continued surveillance and further studies need to be conducted to better understanding on PCV10 vaccine impact.

A strain-independent method to induce progressive and lethal pneumococcal pneumonia in neutropenic mice.

BackgroundExperimental models of pneumonia with penicillin non-susceptible Streptococcus pneumoniae (PNSSP) are hard to reproduce because the majority of strains with clinical relevance (like serotypes 6B, 9 V and 19 F) have low murine virulence. By optimization of culture and inoculum conditions of PNSSP (using porcine mucin), our aim was to develop a suitable, reliable and reproducible pneumonia mouse model for anti-infective pharmacology research.ResultsSeven PNSSP strains, including serotypes 6B, 9 V, 14 and 19 F were included. Strain INS-E611 displayed the highest murine virulence and was chosen to validate the lung model. Nose-instilled pneumococci grew between 2.1 and 2.5 log10 CFU/g of lung in 24 hours when an optimized culture of bacterial cells was used, but animals were all alive and recovered of infection after 36 h. In contrast, inoculum supplementation with mucin led to 100% mortality related to a successful lung infection confirmed by histopathology. These findings were reproduced with all seven PNSSP strains in neutropenic mice. Immunocompetent animals cleared all strains spontaneously.ConclusionsThis pneumonia model produces a progressive and uniformly fatal lung infection with diverse serotypes of PNSSP independently of their intrinsic murine virulence.

Exploring the association between resistance and outpatient antibiotic use expressed as DDDs or packages

The objective of this study was to explore the association between resistance and outpatient antibiotic use, expressed as either DDDs per 1000 inhabitants per day (DID) or packages per 1000 inhabitants per day (PID). IMS Health data on outpatient penicillin and cephalosporin (β-lactam) and tetracycline, macrolide, lincosamide and streptogramin (TMLS) use, aggregated at the level of the active substance (WHO version 2011) expressed as DID and PID (2000-07) were linked to European Antimicrobial Resistance Surveillance System (EARSS) data on proportions of penicillin-non-susceptible Streptococcus pneumoniae (PNSP) and erythromycin-non-susceptible S. pneumoniae (ENSP) (2000-09). Combined data for 27 European countries were analysed with a generalized linear mixed model. Model fit for use in DID, PID or both and 0, 1 or 2 year time lags between use and resistance was assessed and predictions of resistance were made for decreasing use expressed as DID, PID or both. When exploring the association between β-lactam use and PNSP, the best model fit was obtained for use in PID without time lag. For the association between TMLS use and ENSP, the best model fit was obtained for use in both PID and DID with a 1 year time lag. PNSP and ENSP are predicted to decrease when use decreases in PID, but not when use decreases in DID. Associations between outpatient antibiotic use and resistance and predictions of resistance were inconsistent whether expressing antibiotic use as DID or PID. We recommend that data on antibiotic use be expressed as PID and that time lags between use and resistance be considered when exploring these associations.

Reprint of: Serotyping and antibiotic susceptibility of Streptococcus pneumoniae strains isolated in Algeria from 2001 to 2010

IntroductionPneumococcal infections are a major public health problem because of the virulence of this bacterium and its ability to develop resistance. Material and methodTwo hundred and ninety-four strains of Streptococcus pneumoniae were isolated from sterile (56.8%) and non-sterile samples (43.2%), from January 2001 to July 2010. ResultsThe interpretation of antibiotic susceptibility testing, according to CLSI criteria (M100-S21 2011), yielded a 25.2% overall resistance to penicillin, with 23.5% of strains isolated from CSF (meningitis), and only 1.7% in other samples. Resistance to cefotaxime was 8.1% (including 4.4% at a high level). The most common serotypes were: 14 (19.5%), 23F (9.7%), 6B (9.3%), 19F (5.4%), and serotype 1 (5%). The percentage of these serotypes isolated from normally sterile sites in children under 5 years of age was 31.25% for 14, 10.4% for 23F, 8.3% for 19F, 6.25% for 6B, and 4.2% for serotype 1. The theoretical vaccinal coverage against invasive infections in children under 2 years of age was 61.5%, 69.2%, and 76.9% for the 7-valent, 10-valent, and 13-valent conjugate vaccines, respectively. Penicillin non-susceptible Streptococcus pneumoniae (PNSP) strains accounted for 67.1, 68.6, and 72.8% for each of these three vaccines. ConclusionThere was a variation of serotype rates compared to previous studies. The increase in pneumococcal antibiotic resistance is concerning, particularly for the treatment of pneumococcal infections in children and infants. Pneumococcal vaccination is not compulsory yet in Algeria.

Changes in drug resistance and distribution of Streptococcus pneumonia infection from 2001 to 2011 in Shenyang area

Objective To investigate the dynamic changes of infectious distribution,current resistant situation of Streptococcus pneumoniae(SP) and resistant to penicillin and other 10 kinds of antibiotics for the guidance of clinical therapy of SP.Methods Bacteria were identified by French BioMerieux API identification system,VITEK 2-COMPACT identification system and Optochin test,bile solubility test.In vitro,drug susceptibility test to penicillin,cefotaxime,and other 10 kinds of antibiotics were conducted with K-B disk diffusion method combined with the concentration gradient method.Drug susceptibility results were analyzed from 2001 to 2011.Results In recent 11 years,SP antimicrobial resistance rate had increased year after year,especially rates of penicillin-resistant and penicillin not-sensitive had increased significantly,rising from 8.3％( in 2001 ) to 72.7％ ( in 2011 ) ( meningitis 86.4％,non-meningitis 59.0％ ).Resistance rate of cefotaxime,belonging to third-generation cephalosporin had already accounted for 54.0％ ( meningitis 64.0％,non-meningitis 44.0％ ) ;and the resistance rate of macrolide antimicrobial was 100％ ; vancomycin-resistant strains and linezolid-resistant strains had not been detected.Conclusion Penicillin non-susceptible SP has accounted for a high percentage,antimicrobial resistance of Streptococcus pneumoniae penicillin,cephalosporins,macrolides are in serious condition.Vancomycin and linezolid should be preferred or the right antibiotics be chosen according to vitro susceptibility results of isolates in clinical treatment of severe infections caused by SP. Key words: Streptococcus pneumoniae; Antimicrobial drugs; Drug resistance; Surveillance

Serotyping and antibiotic susceptibility of Streptococcus pneumoniae strains isolated in Algeria from 2001 to 2010

IntroductionPneumococcal infections are a major public health problem because of the virulence of this bacterium and its ability to develop resistance. Material and methodTwo hundred and ninety-four strains of Streptococcus pneumoniae were isolated from sterile (56.8%) and non-sterile samples (43.2%), from January 2001 to July 2010. ResultsThe interpretation of antibiotic susceptibility testing, according to CLSI criteria (M100-S21 2011), yielded a 25.2% overall resistance to penicillin, with 23.5% of strains isolated from CSF (meningitis), and only 1.7% in other samples. Resistance to cefotaxime was 8.1% (including 4.4% at a high level). The most common serotypes were: 14 (19.5%), 23F (9.7%), 6B (9.3%), 19F (5.4%), and serotype 1 (5%). The percentage of these serotypes isolated from normally sterile sites in children under 5 years of age was 31.25% for 14, 10.4% for 23F, 8.3% for 19F, 6.25% for 6B, and 4.2% for serotype 1. The theoretical vaccinal coverage against invasive infections in children under 2 years of age was 61.5%, 69.2%, and 76.9% for the 7-valent, 10-valent, and 13-valent conjugate vaccines, respectively. Penicillin non-susceptible Streptococcus pneumoniae (PNSP) strains accounted for 67.1, 68.6, and 72.8% for each of these three vaccines. ConclusionThere was a variation of serotype rates compared to previous studies. The increase in pneumococcal antibiotic resistance is concerning, particularly for the treatment of pneumococcal infections in children and infants. Pneumococcal vaccination is not compulsory yet in Algeria.

Expansion and evolution of the Streptococcus pneumoniae Spain9V-ST156 clonal complex in Poland.

In this study, we analyzed 118 penicillin-nonsusceptible Streptococcus pneumoniae (PNSP) isolates (MICs, >or=0.12 microg/ml) recovered in Poland in 2003 to 2005 from patients with respiratory tract diseases and invasive infections. Seven different serotypes (14, 9V, 23F, 19F, 6B, 19A, and 6A, in order of descending frequency), seven alleles of the murM gene (murMA, murMB6, and the new murMB12 to -16 alleles), and 31 multilocus sequence types (STs) were observed. The vast majority of the PNSP isolates (90.7%) belonged to the international multiresistant clones, and among these, the Spain(9V)-ST156 clonal complex was the most prevalent (56 isolates) and was significantly overrepresented in invasive infections. The clone has been evolving rapidly, as demonstrated by the observed number of STs, the diversity in multiple-locus variable-number-tandem-repeat analysis (MLVA) types, and the polymorphism of pbp and pspA genes (coding for penicillin-binding proteins and the pneumococcal surface protein A, respectively). The presence and structure of the rlrA islet (encoding the pneumococcal pilus) were very well conserved. The Spain(9V)-ST156 clonal complex has been largely responsible for a decreasing susceptibility to penicillin among pneumococci in Poland in recent years, in spite of a relatively moderate antimicrobial use.

Comparison of three different PCR-based methods to predict the penicillin nonsusceptibleStreptococcus pneumoniaeisolates from China

To find a quick and reliable diagnostic technique for penicillin nonsusceptible Streptococcus pneumoniae (PNSSP) from Nanjing, China. A total of 130 S. pneumoniae clinical isolates and 50 healthy carriers' isolates were collected from seven teaching hospitals in Nanjing between March 2005 and June 2007. Three different methods, PCR, seminested-PCR, and PCR-RFLP, were applied in detecting PNSSP. The prevalence of PNSSP was 73.9%, the penicillin-resistance rate of children's group and adults' group were 87.8% and 31.2%, respectively. The PCR method had difficulty in identifying intermediate-resistant and resistant isolates, the PCR-RFLP method could only be used for susceptible isolates and had poor sensitivity. Seminested-PCR was fast, sensitive for detection, and successfully differentiated between moderately and highly resistant S. pneumoniae; 96.1% of the PCR results were in agreement with the minimum inhibitory concentration (MIC) data. The penicillin resistance rate in isolates from children was much higher than of isolates from adults in China. Seminested-PCR for pbp1A was the best diagnostic method. We compared three different strategies for the first time in identification of PNSSP in China. In conclusion, seminested-PCR can be applied in clinical microbiology laboratories for detection of serious infections caused by S. pneumoniae.

Investigation and control of a cluster of penicillin non-susceptible Streptococcus pneumoniae infections in a care home

Two elderly residents of a care home were hospitalised with pneumonia over a period of one month. They had bacteraemia with penicillin non-susceptible Streptococcus pneumoniae (PNSP) and both died. All residents and staff of the care home were screened for PNSP using nasopharyngeal swabs, with one resident and one member of staff found to be asymptomatic carriers. Oral rifampicin was given to the carriers. All four strains were found to be serotype 14, and multilocus sequence typing (MLST) showed ST2652, not previously detected in Scotland. Review of care home residents showed that pneumococcal vaccination coverage was low (63%). This is similar to rates found in those aged > or =65 years in the general population and needs to be improved upon.

Pneumococci responsible for invasive disease and discharging ears in children in Sydney, Australia

The serotypes and molecular clones of penicillin-nonsusceptible Streptococcus pneumoniae (PNSP) responsible for invasive pneumococcal disease (IPD) and discharging ears in metropolitan New South Wales were characterized to form a baseline prior to introduction of the heptavalent conjugate pneumococcal vaccine in Australia. Pneumococci isolated between 1 July 2000 and 30 June 2003 in Sydney from children <15 years were tested for antibiotic susceptibilities and serotyped. Penicillin-nonsusceptible pneumococci were typed by multilocus sequence typing and BOX PCR. During this period, 97 (13.9 %) of 698 pneumococci from IPD that were serotyped were penicillin-nonsusceptible. Of 607 pneumococci from discharging ears, 157 (26.1 %) were penicillin-nonsusceptible. Serotype 14 was the predominant serotype responsible for IPD and serotype 19F predominated from discharging ears. The heptavalent vaccine serotypes accounted for 613 (87.8 %) of all invasive isolates and 420 (69.8 %) of all isolates from discharging ears. Representatives of the major international clones were present among the PNSP. The majority of serotypes and clones that showed penicillin-nonsusceptibility are present within the vaccine. Serotype switching was also noted to have occurred prior to introduction of the vaccine. This study provides a characterization of the pneumococcal serotypes associated with IPD and discharging ears that will be useful for detecting potential selective effects of the vaccine. This surveillance should be continued, as it will be important to monitor the frequency and distribution of serotypes in the post-vaccine era.

Age- and Serogroup-Related Differences in Observed Durations of Nasopharyngeal Carriage of Penicillin-Resistant Pneumococci

Using data from an ongoing Swedish intervention project, the observed durations of nasopharyngeal carriage of penicillin-nonsusceptible Streptococcus pneumoniae (PNSP) (MIC of penicillin G of >or=0.5 microg/ml) stratified by both pneumococcal serogroup and age of the carrier were compared. The means and 95% confidence intervals (CIs) were estimated by fitting a gamma distribution to the observed duration of carriage for each age and serogroup stratum. The mean observed duration of carriage for all cases was 37 days (95% CI, 35 to 38 days). Children below the age of 5 years carried PNSP for significantly longer periods (43 days; 95% CI, 41 to 45 days) compared with older individuals (25 days; 95% CI, 24 to 27 days). There were also differences within the group of cases below the age of 5 years, as the duration of carriage became significantly shorter for each increasing age step: <1, 1 to 2, and 3 to 4 years. In addition, patients <5 years of age carried serogroups 9 and 14 for significantly shorter periods than groups 6 and 23. Serogroup 9 was also carried for significantly shorter periods than group 19. For patients aged 5 years or older, no significant difference in carriage duration for different ages or serogroups could be noted. As young children have the longest duration of PNSP carriage, interventions aiming to reduce the prevalence in this group are of great importance. The results highlight the importance of taking both serogroup and age of the carriers into account when studying the dynamics of pneumococcal transmission in young children.

Clinical observation of meningitis caused by penicillin-susceptible and -non-susceptibleStreptococcus pneumoniaein Taiwanese children

To compare differences between clinical features and outcome in bacterial meningitis caused by penicillin-susceptible Streptococcus pneumoniae (PSSP) with that caused by penicillin-non-susceptible Streptococcus pneumoniae (PNSP). All patients <18 yrs hospitalised with pneumococcal meningitis between January 1984 and December 2002 at Chang Gung Children's Hospital, Taipei were reviewed retrospectively. There were 28 PNSP (63.6%) and 16 PSSP cases of meningitis eligible for the study. The incidence of PNSP meningitis increased significantly over the 8-yr period (p = 0.007). Age <4 yrs (78.6% vs 50%), a lower initial white blood count (mean 11.7 vs 19.9 x10(9)/L), admission to the intensive care unit (70.4% vs 50%) and mortality (28.6% vs 6.3%) were more common in the PNSP group. However, the only significant finding was a lower proportion of polymorphic neutrophils in the CSF of the PNSP meningitis group (p = 0.04). There was an increase in PNSP isolates from patients with meningitis over the 8-yr study period. No major differences were observed in clinical or laboratory features or outcome between the PSSP and PNSP groups.