Streptococcus Pneumoniae Strains Research Articles

Antimicrobial susceptibility and serotype distribution of Streptococcus pneumoniae isolates among children in Suzhou, China.

Streptococcus pneumoniae (SP) is responsible for pneumococcal diseases with severe morbidity and mortality. High rates of drug resistance constitute serious public health concerns. Vaccination has proven to be an effective means of reducing disease burden. Epidemiological information of antibiotic susceptibilities and serotype distribution will be of great help to the management of pneumococcal infections. This study reported the serotype distribution and antibiotic resistance pattern of SP in hospitalized children in Suzhou during the years 2017-2018. The aim is to reduce pneumococcal resistance and guide vaccination. The clinical data of hospitalized children with SP were collected and analyzed. A total of 2,446 strains of SP were isolated from these patients. Serotypes were determined using the Quellung reaction. Antibiotic resistance was tested using the E-test diffusion method. The non-susceptible rates of the isolates to penicillin, amoxicillin, and cefotaxime were 9.5%, 27.7%, and 27.2%, respectively. And 97.6% of SP isolates showed multidrug-resistant (MDR). The most common resistance pattern of non-invasive isolates was macrolides + sulfamethoxazole + clindamycin + tetracycline. The major serotypes of this resistance pattern were 6A, 23F, 6B, 19F, 15B. The most extensive resistance pattern of invasive isolates was macrolides + β-lactams + sulfamethoxazole + clindamycin + tetracycline. The most common serotypes of the pattern were 19F, 19A, 6B, 23F, 6A. The most common serotypes were 19F (28.6%), 6B (11.9), 23F (11.2%), 6A (10.6%), and 19A (9.1%). In the isolates with MDR, the first five most common serotypes were 19F, non-vaccine serotype (NVT), 6B, 6A and 23F. Strains belonging to different serotypes exhibited distinct antimicrobial resistance patterns and were found to be associated with different diseases. The coverage rates of pneumococcal conjugate vaccine (PCV)7 and PCV13 in all isolates reached 60.4% (310/513) and 80.9% (415/513), respectively. The main serotypes of SP in Suzhou were 19F, 6B, 23F, 6A, and 19A. The use of PCV13 is beneficial to children in Suzhou.

In silico Studies on Potential Inhibitors of the Penicillin Binding Protein 2B (PBP2B) of the Resistant G54 and Intermediate-resistant Hungary 19A-6 and SP195 Strains of Streptococcus Pneumoniae

Background: Mutations in Penicillin Binding Protein 2B (PBP2B) lead to resistance against commercial β-lactam antibiotics among some strains of Streptococcus pneumoniae. In this study, the molecular mechanism of resistance and the alternate strategy for controlling the Penicillin Binding Protein 2B (PBP2B) of resistant G54 and the two intermediate-resistant Hungary19A-6 and SP195 strains of Streptococcus pneumoniae are determined using an in silico approach. Methods: In this study, we considered four ligand compounds, namely ZINC59376795, ZINC36922620, ZINC39550705, and ZINC36953975 of the ZINC database, identified through high-throughput screening (HTS) study for the resistant strain (5204-PBP2B). Glide XP docking and molecular dynamic simulation studies were performed on the PBP2B of the three resistant strains chosen for this study. The stability analysis was performed with prime-MM/GBSA, and the binding free energy, RMSD, and RMSF were also evaluated. Results: Out of the four ligands, the ZINC39550705 ligand was found to form a stable complex with PBP2B of all three strains. Furthermore, this ZINC39550705 ligand was observed to form four hydrogen bonds with the PBP2B of all three strains. Molecular dynamics simulations were performed with these four selected ligands and targets. The resulting binding pattern, RMSD, RMSF, and hydrogen bond calculation analyses provide deeper insight into the molecular interactions of these four selected ligands with the PBP2B of the three resistance strains of S. pneumoniae. Conclusion: The interaction of the selected ligand molecules and PBP2B of the resistant strains of S. pneumoniae revealed that hydroxyl amino acid Thr at position 224, acidic amino acids including Glu at positions 301, 245, and 240, amidic amino acids, Asn at positions 265 and 260, and aliphatic amino acid Gly at the 302 position had a crucial role in the formation of hydrogen bonds with most of the selected ligands that contributed to the stability of the complexes. The molecular dynamics simulation further confirmed that the stability of ligand ZINC39550705–PBP2B of all mutant strains was higher compared to other ligand-protein complexes evaluated in the present study. Selected ligand molecules showed significant properties of the inhibitor to be used against the resistant strains of S. pneumoniae, and the ligand ZINC39550705, in particular, is a potential alternative to commercial β-lactam antibiotics.

Microparticulation of Levofloxacin HCl by Crystallo-co-agglomeration Technique

Particle engineering techniques have gained a unique place in the present pharma industry to improve physicochemical properties of the drugs. The aim of this research work was to formulate and evaluate directly compressible agglomerates of Levofloxacin HCl with a view to improve their micromeritic properties and thereby to reduce the cost of production. Fluoroquinolone anti-infective, is used to treat bacterial conjunctivitis, sinusitis, chronic bronchitis, community- acquired pneumonia and pneumonia caused by penicillin resistant strains of Streptococcus pneumonia. Some of the fluoroquinolone high dose’s exhibit poor compressibility and flow properties, hence may not be suitable candidate for direct compression process, but by applying the crystallo-co-agglomeration (CCA) technique, the attempt may be made to change the properties of these molecules to make them suitable candidates for direct compression. This investigation was aimed to utilize CCA process to develop spherical agglomerates of levofloxacin HCl in selected polymers in different ratio. The developed spherical agglomerates of levofloxacin HCl may exhibit improved micrometric and dissolution properties hence may be suitable for direct compression process. Results indicated that micromeritic, mechanical and compressional properties of the agglomerates were greatly influenced by nature and type of polymer incorporated. The mean release time, mean dissolution time, dissolution efficiency, Q30 and Q90 of the tablets prepared from agglomerates showed remarkable increase in CCA compared to tablets prepared by wet granulation. Observations also revealed that by varying the type and concentration of polymer, desired release rate can be obtained.

Prevalence and antimicrobial resistance profiles of respiratory microbial flora in African children with HIV-associated chronic lung disease

BackgroundHIV-associated chronic lung disease (CLD) is common among children living with HIV (CLWH) in sub-Saharan Africa, including those on antiretroviral therapy (ART). However, the pathogenesis of CLD and its possible association with microbial determinants remain poorly understood. We investigated the prevalence, and antibiotic susceptibility of Streptococcus pneumoniae (SP), Staphylococcus aureus (SA), Haemophilus influenzae (HI), and Moraxella catarrhalis (MC) among CLWH (established on ART) who had CLD (CLD+), or not (CLD-) in Zimbabwe and Malawi.MethodsNasopharyngeal swabs (NP) and sputa were collected from CLD+ CLWH (defined as forced-expiratory volume per second z-score < − 1 without reversibility post-bronchodilation with salbutamol), at enrolment as part of a randomised, placebo-controlled trial of azithromycin (BREATHE trial - NCT02426112), and from age- and sex-matched CLD- CLWH. Samples were cultured, and antibiotic susceptibility testing was conducted using disk diffusion. Risk factors for bacterial carriage were identified using questionnaires and analysed using multivariate logistic regression.ResultsA total of 410 participants (336 CLD+, 74 CLD-) were enrolled (median age, 15 years [IQR = 13–18]). SP and MC carriage in NP were higher in CLD+ than in CLD- children: 46% (154/336) vs. 26% (19/74), p = 0.008; and 14% (49/336) vs. 3% (2/74), p = 0.012, respectively. SP isolates from the NP of CLD+ children were more likely to be non-susceptible to penicillin than those from CLD- children (36% [53/144] vs 11% [2/18], p = 0.036). Methicillin-resistant SA was uncommon [4% (7/195)]. In multivariate analysis, key factors associated with NP bacterial carriage included having CLD (SP: adjusted odds ratio (aOR) 2 [95% CI 1.1–3.9]), younger age (SP: aOR 3.2 [1.8–5.8]), viral load suppression (SP: aOR 0.6 [0.4–1.0], SA: 0.5 [0.3–0.9]), stunting (SP: aOR 1.6 [1.1–2.6]) and male sex (SA: aOR 1.7 [1.0–2.9]). Sputum bacterial carriage was similar in both groups (50%) and was associated with Zimbabwean site (SP: aOR 3.1 [1.4–7.3], SA: 2.1 [1.1–4.2]), being on ART for a longer period (SP: aOR 0.3 [0.1–0.8]), and hot compared to rainy season (SP: aOR 2.3 [1.2–4.4]).ConclusionsCLD+ CLWH were more likely to be colonised by MC and SP, including penicillin-non-susceptible SP strains, than CLD- CLWH. The role of these bacteria in CLD pathogenesis, including the risk of acute exacerbations, should be further studied.

In Vitro Activity of the Novel Lactone Ketolide Nafithromycin (WCK 4873) against Contemporary Clinical Bacteria from a Global Surveillance Program.

Nafithromycin (WCK 4873), a novel antimicrobial agent of the lactone ketolide class, is currently in phase 2 development for treatment of community-acquired bacterial pneumonia (CABP). A total of 4,739 nonduplicate isolates were selected from a 2014 global surveillance program at medical institutions located in 43 countries within the United States, Europe, Latin America, and the Asia-Pacific region. Nafithromycin and comparator agents were used for susceptibility testing by reference broth microdilution methods. Nafithromycin was active against Staphylococcus aureus (MIC50/90, 0.06/>2 μg/ml), including erythromycin-resistant strains exhibiting an inducible clindamycin resistance phenotype (MIC50/90, 0.06/0.06 μg/ml) and telithromycin-susceptible strains (MIC50/90, 0.06/0.06 μg/ml), but it exhibited limited activity against most telithromycin-resistant and clindamycin-resistant isolates that were constitutively resistant to macrolides (MIC50/90, >2/>2 μg/ml). Nafithromycin was very active (MIC50/90, 0.015/0.06 μg/ml) against 1,911 Streptococcus pneumoniae strains, inhibiting all strains, with MIC values of ≤0.25 μg/ml. Telithromycin susceptibility was 99.9% for Streptococcus pneumoniae strains, and nafithromycin was up to 8-fold more potent than telithromycin. Overall, 37.9% of S. pneumoniae strains were resistant to erythromycin, and 19.7% were resistant to clindamycin. Nafithromycin was highly active against 606 Streptococcus pyogenes strains (MIC50/90, 0.015/0.015 μg/ml), inhibiting 100.0% of isolates at ≤0.5 μg/ml, and MIC50/90 values (0.015/0.015 to 0.03 μg/ml) were similar for the 4 geographic regions. Nafithromycin and telithromycin demonstrated comparable in vitro activities against 1,002 Haemophilus influenzae isolates and 504 Moraxella catarrhalis isolates. Overall, nafithromycin showed potent in vitro activity against a broad range of contemporary (2014) global pathogens. These results support the continued clinical development of nafithromycin for treatment of CABP.

Antibiotic resistance of Streptococcus pneumoniae, isolated from nasopharynx of preschool children with acute respiratory tract infection in Lithuania.

BackgroundIncreasing pneumococcal resistance to commonly used antibiotics and multidrug resistance is a serious public health concern. Data on distribution of resistant Streptococcus pneumoniae (SPn) strains among children in Lithuania are limited. We evaluated the circulation of SPn serotypes and antimicrobial susceptibility among preschool children in Lithuania before the introduction of universal infant pneumococcal vaccination.MethodsA prospective study was carried out from February 2012 to March 2013 in five cities of Lithuania. A total of 900 children under six years of age who presented to primary care centre or a hospital emergency department with acute respiratory tract infection were enrolled in the study. Nasopharyngeal swabs were obtained and cultured for SPn. Positive samples (n = 367) were serotyped and tested for antimicrobial susceptibility. Associations of pneumococcal non-susceptibility with study site, season, age, sex, attendance of day care centre and treatment with antimicrobials (between one and six months prior the study) were evaluated.ResultsAbout a half (56.7 %) of SPn strains were susceptible to all the antibiotics tested. Pneumococcal non-susceptibility to penicillin, erythromycin, clindamycin and trimethoprim–sulphamethoxazole was 15.8, 21.3, 16.9 and 27.3 %, respectively. None of the tested isolates was resistant to norfloxacin or vancomycin. We found a geographical variation of pneumococcal resistance within the cities of the country. Age, sex, the attendance of day care centre and treatment with antimicrobials prior the study was not significantly associated with a carriage of non-susceptible SPn strains. Among non-susceptible SPn serotypes 67.9 %–82.4 % were present in currently available pneumococcal conjugate vaccines.ConclusionsThe rates of nasopharyngeal SPn susceptibility to penicillin and macrolides are still high among preschool children in Lithuania, however they are lower compared with previous studies. A strict policy with respect to antibiotic prescription together with widespread use of vaccination could potentially reduce the carriage rate of antibiotic-resistant pneumococci in our country.

Distribution and drug resistance of the pathogenic bacteria from sputum specimens of 1 125 children with tracheo bronchial foreign bodies

To analyze the distribution and drug susceptibility of the pathogenic bacteria in the airway secretions in children with tracheobronchial foreign bodies so as to assist physicians in clinical prescription. Sputum specimens of 1 125 children with tracheobronchial foreign bodies were collected in removal of the foreign bodies by rigid bronchoscope, and the drug susceptibility test was performed. Pathogenic bacteria were detected in 218 (19.4%) of 1 125 sputum specimens. Among the pathogenic bacteria, 126 (57.79%) strains were gram-negative bacilli, consisting of 76 (34.86%) strains of Haemophilus influenzae, 10 (4.59%) strains of Escherichia coli, 7 (3.21%) strains of Sewer enterobacter, 7 (3.21%) strains of Pseudomonas aeruginosa, and 6 (2.75%) strains of Klebsiella bacillus; and 92 (42.21%) strains were gram-positive bacilli, consisting of 80 (36.69%) strains of Streptococcus pneumonia and 10 (4.59%) strains of Escherichia coli. Most of detected gram-negative bacilli were highly sensitive to cefepime, ceftazidine, imipenem and amikacin, no strains were resistant to meropenem and ciprofloxacin. None of the detected gram-positive bacilli were resistant to cefepime, vancomycin, levofloxacin and teicoplanin. The Haemophilus influenzae of gram-negative bacilli and the Streptococcus pneumonia of gram-positive bacilli are the main pathogenic bacteria existing in the airway secretions of children with tracheobronchial foreign bodies. The Haemophilus influenzae were highly sensitive to cephalosporin, imipenem and amikacin, and the Streptococcus pneumonia to cefepime, vancomycin, levofloxacin and teicoplanin.

Serotyping and Antimicrobial Resistance Pattern of Streptococcus Pneumoniae Strains in Patients with Community-Acquired Pneumonia

Serotyping and Antimicrobial Resistance Pattern of Streptococcus Pneumoniae Strains in Patients with Community-Acquired Pneumonia

Invasive Pneumococcal Disease (IPD) Serotype Frequency in Iranian Patients.

BackgroundStreptococcuspneumoniae as a Gram positive diplococcic is a major worldwide causative agent of morbidity and mortality among young children and the aged. In addition, Streptococcus pneumoniae is a versatile human pathogen causing infectious disease ranging from mild infection (i.e. otitis media) to life therating pneumonia and meningitidis in many countriesObjectivesThe aim of this study was to determine the frequency type of Streptococcuspneumoniae in Invasive pneumococcal disease (IPD) in Iranian patients.Patients and MethodsA total of 135 Streptococcuspneumoniae strains were isolated from patients infectious suspected of invasive streptococcal disease. They were subjected to PCR and bacteriological methods. Out of which, 134 strains of S. pneumoniae were serotyped and confirmed by PCR method. The data were analyzed by SPSS version 17.0.ResultsThe results of this study showed some S. pneumoniae serotypes were found in both sexes and some only in one sex invasive infections. For example, serotypes 10, 14, 18 and 22 were only in female patients with infections.ConclusionsThe analysis of the results had suggested that serotypes 6 from Lung and 19 from Eye are the most abundant bacterial strains isolated from patients. The diseases could be prevented by using the Pneumococcal vaccine.

Serotype discrimination of encapsulated Streptococcus pneumoniae strains by Fourier-transform infrared spectroscopy and chemometrics

Fourier-transform infrared (FTIR) spectroscopy was evaluated as an alternative method for serotyping encapsulated Streptococcus pneumonia strains. Sixty-nine invasive strains from the Microbiology Laboratory of the Medicine Faculty of University of Lisbon were selected for the analysis. The encapsulated strains used in this work (9N, 9V, 14, 19A, 19F, 23A, 23B and 23F) were serotyped by the standard capsular reaction test using the chessboard method and specific sera. FTIR spectra were analysed with chemometric methods. Results showed that the best spectral region unveiling serotype difference is located at 1185–900cm−1. A partial least squares discriminant analysis model was calibrated using this spectral region against the chessboard method serotyping. FTIR spectroscopy proved to be able to correctly predict 100% of strains according to the serogroups (9, 14, 19, 23). A segregated analysis showed that it was also possible to differentiate serotypes belonging to the same serogroup although spectral differences are less pronounced as was initially expected.

Levofloxacin for the treatment of respiratory tract infections

Introduction: Fluoroquinolone use has dramatically increased since the introduction of the first respiratory fluoroquinolone in the late 1990s. Levofloxacin, like other fluoquinolones, is a potent antibiotic, due to high levels of susceptibility among Gram-negative, Gram-positive (including penicillin-resistant strains of Streptococcus pneumonia) and atypical pathogens. Levofloxacin is recommended for the treatment of community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP) and in the management of acute exacerbations of chronic bronchitis (AECB). Levofloxacin demonstrates good safety, bioavailability and tissue penetration, thus maintaining adequate concentrations at the site of infection. High-dose (750 mg), short-course (5 days) therapy regimens may offer improved treatment, especially in HAP, due to higher drug concentrations, increased adherence and the potential to reduce the development of resistance.Areas covered: This article covers medical literature published in any language since 1990 until November 2011, on ‘levofloxacin’, identified using PubMed and MEDLINE. The search terms used were ‘levofloxacin’ and ‘community acquired pneumonia’, ‘hospital pneumonia’ or ‘AECB’.Expert opinion: Levofloxacin is a valuable antimicrobial agent and an optimal treatment option for AECB, CAP (as a monotherapy) and HAP (as combination therapy at a high-dose regimen). Its improved bioavailability and safety profile makes the possibility of shorter hospital stays a reality.

Clinical features of invasive pneumococcus with resistance to antimicrobial agents in Pediatric Intensive Care Unit

Objective To study the clinical features of invasive pneumococcus disease (IPD) with resistance to antimicrobial agents in children,and to improve the diagnosis and treatment of this disease.Methods The clinical data from 21 IPD patients younger than 13 years old were collected from January 2008 through December 2010 in Pediatric Intensive Care Unit in Beijing Children's Hospital for retrospective analysis. Specimens of blood,pleural effusion,cerebrospinal fluid and soft tissue aspirated were collected from these children,and 23 strains of streptococcus pneumonia (SP) were cultured,isolated and confirmed,and the antibiotics susceptibility to penicillin and other antibiotics of these strains were assayed.Results Among the 21 IPD children,the ratio of male to female was 0.9∶1,and the age was 5 months to 13 years,with 61.9％ of them under 2 years.Of them,12 patients (57.1％ ) had purulent pleurisy,and 1 (4.8％ )patient had an underlying disease diagnosed to be X - linked agammaglobulinemia (XLA).There was no seasonal difference in the occurrence rate of this disease. Eight (38.1％) patients were cured,11(52.4％ ) were improved,while 2 (9.5％ ) patients not improved without death.There was no statistically significant difference in the annual detection rate of invasive SP (x2 =3.711,P =0.156).The incidences of penicillin-intermediate susceptibility SP (PISP) and penicillin-resistant SP (PRSP) were 47.8％ and 26.1％ respectively.The rate of resistance to multiple antibiotics was 91.3％.Conclusions Children aged less than 5 years,especially younger than 2 years,are prone to IPD,and purulent pleurisy and septicemia are often seen in this disease. Some patients had the underlying diseases.The complications included hemophagocytic syndrome,acute respiratory distress syndrome,septic shock,bronchial pleural fistula and so on.The multidrug resistance rate was 91.3％.It is important to put great emphasis on the monitoring antibiotics resistance to invasive pneumococcal disease. Key words: Invasive pneumococcal disease; Pediatric Intensive Care Unit; Drug resistance; Retrospective studies

Biofilm Potential of Common Otopathogens

Objective: Posttympanostomy tube (TT) otorrhea has been linked to microbial biofilms. TTs may be exposed to a wide range of microbes. The purpose of this study was to compare the TT-biofilm forming propensity of common otopathogens, Pseudomonas aeruginosa (PA), Staphylococcus aureus (SA), Haemophilus influenzae (HI), and Streptococcus pneumoniae (SP). Method: Fluoroplastic coupons were exposed to plasma and cultured with 3 strains of PA, SA, HI, or SP for 2, 4, or 7 days. Half of the coupons were treated with antibiotics to kill planktonic bacteria. Total and biofilm colony counts and electron microscopy were performed. Results: SA formed mature biofilm after 2 days, not different from 4- or 7-day biofilms ( P &gt; .05), and was most tolerant to antibiotic treatment. PA also formed biofilms at 2 days, reached a plateau at 4 days ( P &gt; .05), and decreased at 7 days ( P &lt; .01). HI formed biofilm only after 4 days ( P ≤ .04). SP did not form biofilm without catalase supplementation. With catalase, one SP strain showed a delay in biofilm formation similar to HI ( P &lt; .0001) while the other 2 strains formed biofilms after 2 days. Conclusion: TT biofilm formation occurs with common middle ear pathogens, but most readily with SA and PA. Further investigation is needed to determine if these findings may in part explain the occasionally refractory nature of post-TT otorrhea associated with SA and PA.

The surface-anchored NanA protein promotes pneumococcal brain endothelial cell invasion

In humans, Streptococcus pneumoniae (SPN) is the leading cause of bacterial meningitis, a disease with high attributable mortality and frequent permanent neurological sequelae. The molecular mechanisms underlying the central nervous system tropism of SPN are incompletely understood, but include a primary interaction of the pathogen with the blood–brain barrier (BBB) endothelium. All SPN strains possess a gene encoding the surface-anchored sialidase (neuraminidase) NanA, which cleaves sialic acid on host cells and proteins. Here, we use an isogenic SPN NanA-deficient mutant and heterologous expression of the protein to show that NanA is both necessary and sufficient to promote SPN adherence to and invasion of human brain microvascular endothelial cells (hBMECs). NanA-mediated hBMEC invasion depends only partially on sialidase activity, whereas the N-terminal lectinlike domain of the protein plays a critical role. NanA promotes SPN–BBB interaction in a murine infection model, identifying the protein as proximal mediator of CNS entry by the pathogen.

Resistant Pneumococci Causing Otitis and Sinusitis Failures

Objective Describe cases of non-responsive otitis media and rhinosinusitis due to highly resistant strains of Streptococcus pneumoniae. Methods Resistant strains of Streptococcus pneumonia were isolated from cases of non-responsive pediatric otitis media or rhinosinusitis, from September 2005 to September 2008, from a single pediatric otolaryngology practice. Children had failed therapy with “high dose” amoxicillin-clavulanate and/or ceftriaxone injections. Results 54 cases of apparent failed therapy were detected. The strain(s) demonstrated in vitro high level resistance to penicillin, amoxicillin-clavulanate, oral cepahalosporins, trimethoprim-sulfamethoxazole, macrolides, and clindamycin; and were intermediately or fully resistant to ceftriaxone. Serotyping of representative isolated demonstrated these to be 19A pneumococcal isolates. These cases were often in unusually young infants, and often were from a single prolonged episode of acute otitis medi, including 2 cases of mastoiditis with subperiostial abscess. Most of the cases were identified by office-based diagnostic tympanocentesis and were rarely isolated from children undergoing tympanstomy tube placement. All cases resolved after therapy with levofloxacin pediatric suspension (25 mg/ml, 20 mg'kg/day divided BID. Conclusions This is the largest series of otitis and sinusitis cases due to these highly resistant organisms; and these cases suggest that resistant pneumoccocci are likely causing a significant number of treatment failures in the U.S. They are not detected unless nasal or middle ear cultures are taken from treatment failures. Treatment with fluoroquinolones is effective, but raises issues concerning the role of this class of anitbiotics in children.

Antibiotic-Resistant Invasive Pneumococcal Clones in Italy

A total of 105 multiple-antibiotic-resistant invasive pneumococcal isolates recovered in Italy from 2001 to 2003 were genetically characterized. Of these, 40 were penicillin-nonsusceptible (PNSSP) and 65 were penicillin-susceptible (PSSP) Streptococcus pneumoniae strains. Among the PNSSP isolates, 8 and 11 different restriction profiles were obtained for the pbp2b and pbp2x genes, respectively. Clonal groups were established on the basis of analysis of both pulsed-field gel electrophoresis (PFGE) types and multilocus sequence typing (MLST). Several international clones, such as Spain(23F)-1/ST81, Spain(6B)-2/ST90, Spain(9V)-3/ST156, and Sweden(15A)-25/ST63 [corrected] were identified among the PNSSP isolates. Other, smaller clones, such as the minor Spanish 19F clone/ST88 and Denmark(14)-32/ST230, were also found. Among the PSSP isolates, clones related to England(14)-9/ST9, Greece(6B)-22/ST273, and Portugal(19F)-21/ST177 were found. In addition, two large clones comprised nonvaccine serotypes. One, comprising serotype 3 isolates, corresponded to the clone Netherlands(3)-31/ST180; the other, comprising serotype 15B/C isolates, ST474, was not related to any previously described clone. Two small clusters related to the newly described clones Greece(21)-30/ST193 and Netherlands(15B)-37/ST199 included isolates with unrelated PFGE profiles. An unusual finding was the inability to obtain the MLST allelic profile for an isolate of serotype 19A, belonging to the Sweden(15A)-25/ST63 [corrected] clone, due to a large deletion of the xpt gene. Capsular switching was observed among both PNSSP and PSSP isolates and involved also serotypes not included in the 7-valent pneumococcal conjugate vaccine (PCV7), such as serotypes 15B/C and 19A. Since antibiotic-resistant nonvaccine serotype clones are present in Italy, continuous monitoring of pneumococcal epidemiology should be carried out in the PCV7 era.

Pulmonary Damage and Bacterial Load in Assessment of the Efficacy of Simulated Human Treatment-Like Amoxicillin (2,000 Milligrams) Therapy of Experimental Pneumococcal Pneumonia Caused by Strains for Which Amoxicillin MICs Differ

An experimental rat pneumonia model using two amoxicillin-susceptible (MICs, < or =0.015 and 2 microg/ml) and two non-amoxicillin-susceptible (MIC, 4 microg/ml) Streptococcus pneumoniae strains was developed for testing the efficacy of amoxicillin administered to simulate human serum kinetics after treatment with amoxicillin-clavulanate (2,000 and 125 mg, respectively, twice a day, for 2.5 days). The end points for efficacy were reductions in bacterial loads in the lungs and reductions in levels of pulmonary damage. For the amoxicillin-susceptible strains (serotypes 23F and 14), a decrease greater than 4.5 log(10) CFU/pair of lungs was obtained, and the time for which the serum antibiotic concentration (SAC) was higher than the MIC (T(S)(A)(C)(>)(MIC)) was greater than 60% of the dosing interval. For non-amoxicillin-susceptible strains, the decrease in bacterial load was 1.34 to 1.75 log(10) CFU/pair of lungs, with a T(S)(A)(C)(>)(MIC) of 46.7% of the dosing interval. An in vitro study showed that serotype 9V non-amoxicillin-susceptible strains behaved as tolerant-like to concentrations similar to those in the in vivo model. The high and maintained SACs (T(S)(A)(C)(>)(MIC), >46% for all strains) significantly diminished lung injury (affected area of the lung and lung weight), compared to that in controls, by all strains, regardless of the MIC, bactericidal behavior in in vitro killing curves, or the serotype of the infecting strain. These results show the importance of host therapeutic end points in the evaluation of antibiotic efficacy. The antibiotic was more efficacious, for one nonsusceptible strain tested, when the treatment was started early (1 h postinoculation [p.i.]) than when treatment was delayed (24 h p.i.).

Invasive pneumococcal infection presenting as septic arthritis and Austrian-like syndrome involving the tricuspid valve in a patient with underlying HIV infection

Invasive pneumococcal infection (IPI) is a re-emerging complication of Streptococcus pneumoniae infection, particularly in patients with human immunodeficiency virus (HIV) infection. We report a case of a patient who presented with pneumococcal septicaemia, meningitis and septic arthritis, which initially responded to antibiotics, but where the patient eventually succumbed to infective endocarditis of the tricuspid valve. We discuss the spectrum of clinical manifestations of IPI, focusing especially on the Austrian syndrome (defined as pneumococcal endocarditis with rupture of the aortic valve and meningitis), its association with HIV infection, and its management in light of the emergence of penicillin-resistant strains of Streptococcus pneumonia.

51 Epidemiology, Serotypes Distribution and Antibiotic Susceptibility of Streptococcus Pneumoniae Strains Associated with Invasive Pneumococcal Diseases in a Pediatric Tertiary Care Center in Montreal

51 Epidemiology, Serotypes Distribution and Antibiotic Susceptibility of Streptococcus Pneumoniae Strains Associated with Invasive Pneumococcal Diseases in a Pediatric Tertiary Care Center in Montreal

Pediatric invasive pneumococcal disease in a teaching hospital in Bangkok

Background: Increased problems with drug-resistant Streptococcus pneumoniae (SP) and the dearth of epidemiologic and clinical information on invasive pneumococcal disease in children in Asia formed the basis for this study. Methods: A periodic retrospective review of the records of 0–15-year-old patients was conducted at a teaching Hospital in Bangkok, during 1971–2000. Results: Infections with penicillin-non-susceptible SP (PNSSP) strains rapidly increased after they first appeared in 1988, and they accounted for 71% (29/41) of the total cases during 1996–2000. Of 137 patients, 74% were <60 months old, and 66% had an underlying condition. Infections included: bacteremia without focus 51; pneumonia 38; meningitis 35; peritonitis 13; and bone/joint infection 2. Two patients had two foci of infection. Eight of 10 episodes in patients with AIDS were bacteremic pneumonia. Median ages (range) in months for patients with and without an underlying condition were 24 (1–174) and 10 (0–160); and for the patients without an underlying condition they were: pneumonia 23 (4–156); bacteremia without focus 12 (0–160); and meningitis 7 (2–156). Case-fatality rates were 18% and 2% for patients with and without an underlying condition. The study also examined factors associated with PNSSP infection and death. During 1991–2000,74% (43/58) of the total cases occurred from November to April, which are dry months. Conclusions: This study population contained a high proportion with both an underlying condition and infection with PNSSP, and a moderately low proportion with bacteremia without focus. The disease was two to three times more common in dry months than in rainy months.