Silvia R. Santos

Serotype distribution of Streptococcus pneumoniae isolated from patients with invasive pneumococcal disease in Brazil before and after ten-pneumococcal conjugate vaccine implementation

The ten-pneumococcal conjugate vaccine (PCV10) was introduced into the national immunization program for childhood vaccination schedules by the Brazilian Health Public Service in March 2010. The aim of this study was to compare Streptococcus pneumoniae serotype distribution, antibiotic resistance patterns, and potential coverage before (January 2006-June 2010) and after (July 2010-September 2012) PCV10 introduction. The incidence of invasive pneumococcal disease (IPD), patient demographics, and disease characteristics were recorded. This study was conducted at the University Hospital of Sao Paulo University in Brazil from January 2006 to September 2012. Serotyping was performed using multiplex PCR typing, and antimicrobial sensitivity by Clinical and Laboratory Standards Institute (CLSI). A total of 259 S. pneumoniae strains were isolated from patients with IPD. The ages of the patients ranged from 3 months to 95 years old. The strains were isolated from cerebrospinal fluid, pleural fluid, and blood. The incidence of IPD among patients at HU-USP changed after the introduction of PCV10. The overall incidence of IPD was 3.42 cases per 1000 admissions in the vaccine pre- implementation period and of 2.99 cases per 1000 admissions in the vaccine post-implementation period. The incidence of IPD among children<2 y.o. attended at HU-USP changed significantly after the introduction of PCV10, from 20.30 to 3.97 of incidence. The incidence of PCV10- serotypes decrease from 16.47 to 0.44 in the same age, before and after PC10 implementation, respectively. Moreover, it was possible to realize the sensitivity to penicillin among isolates increased significantly in the post-vaccine period. Data from this study suggest that PCV10 contributed to decrease with PID rate among children less than 2 y.o. The resistance rate among pneumococcal isolates also could be observed since serotypes with greater resistance to beta lactam antibiotics were not easily isolated after vaccination.

Negative effects of famotidine on cardiac performance assessed by noninvasive hemodynamic measurements

In a randomized placebo-controlled study 12 healthy volunteers were treated for 1 wk each with 10 mg of nifedipine four times daily plus placebo or the same dose of nifedipine concurrently with 40 mg of famotidine once a day. Famotidine did not significantly alter pharmacokinetic parameters of nifedipine. Determination of systolic time intervals showed that the preejection period and the ratio of the preejection period and the left ventricular ejection time were significantly reduced by administration of nifedipine plus placebo. Coadministration of famotidine and nifedipine, however, led to a significant increase of these parameters. In an additional double-blind study, a significant rise of the preejection period and of the ratio was detected after administration of famotidine alone. In impedance cardiography stroke volume and cardiac output were significantly reduced by famotidine. Heart rate and blood pressure values were not altered by the H2-antagonist. For the first time, to our knowledge, the observed changes of hemodynamic parameters appear to indicate that famotidine may exert negative effects on cardiac performance which, in our opinion, could be of clinical relevance in elderly subjects or in patients with heart failure.

Extended-spectrum beta-lactamases among Enterobacteriaceae isolated in a public hospital in Brazil

Extended-spectrum beta-lactamases (ESBL) in enterobacteria are recognized worldwide as a great hospital problem. In this study, 127 ESBL-producing Enterobacteriaceae isolated in one year from inpatients and outpatients at a public teaching hospital at São Paulo, Brazil, were submitted to analysis by PCR with specific primers for bla SHV, bla TEM and bla CTX-M genes. From the 127 isolates, 96 (75.6%) Klebsiella pneumoniae, 12 (9.3%) Escherichia coli, 8 (6.2%) Morganella morganii, 3 (2.3%) Proteus mirabilis, 2 (1.6%) Klebsiella oxytoca, 2 (1.6%) Providencia rettgeri, 2 (1.6%) Providencia stuartti, 1 (0.8%) Enterobacter aerogenes and 1 (0.8%) Enterobacter cloacae were identified as ESBL producers. Bla SHV, bla TEM and bla CTX-M were detected in 63%, 17.3% and 33.9% strains, respectively. Pulsed field gel eletrophoresis genotyping of K. pneumoniae revealed four main molecular patterns and 29 unrelated profiles. PCR results showed a high variety of ESBL groups among strains, in nine different species. The results suggest the spread of resistance genes among genetically different strains of ESBL-producing K. pneumoniae in some hospital wards, and also that some strongly related strains were identified in different hospital wards, suggesting clonal spread in the institutional environment.

Analysis of invasive pneumonia-causing strains of Streptococcus pneumoniae: serotypes and antimicrobial susceptibility

OBJECTIVES To identify the most common pneumococcal serotypes in children hospitalized with invasive pneumonia, correlate isolated serotypes with those included in conjugate vaccines, and ascertain the sensitivity of the isolated pneumococcal strains to penicillin and other antibiotics. METHODS From January 2003 to October 2008, a retrospective study of hospitalized children with a diagnosis of Streptococcus pneumoniae pneumonia was conducted at the university hospital of Universidade de São Paulo. Criteria for inclusion were: age greater than 29 days and less than 15 years, radiological and clinical diagnosis of pneumonia, and isolation of Streptococcus pneumoniae in blood cultures and/or pleural effusion. RESULTS The study included 107 children. The most common serotypes were 14 (36.5%), 1 (16%), 5 (14.6%), 6B (6.3%) and 3 (4.2%). The proportion of identified serotypes contained in the heptavalent, 10-valent and 13-valent conjugate vaccines was 53.1, 86.5, and 96.9%, respectively. Pneumococcal strains were sensitive to penicillin (minimum inhibitory concentration, MIC ≤ 2 µg/mL) in 100 cases (93.5%) and displayed intermediate resistance (MIC = 4 µg/mL) in 7 cases (6.5%). No strains were penicillin-resistant (MIC ≥ 8 µg/mL) according to the Clinical and Laboratory Standards Institute 2008 standards. Tested isolates were highly sensitive to vancomycin, rifampicin, ceftriaxone, clindamycin, erythromycin, and chloramphenicol. CONCLUSIONS Our results confirm a significant potential impact of conjugate vaccines, mainly 10-valent and 13-valent, on invasive pneumonia. Furthermore, susceptibility testing results show that penicillin is still the treatment of choice for invasive pneumonia in our setting.

Cross-Reactivity of Antipneumococcal Surface Protein C (PspC) Antibodies with Different Strains and Evaluation of Inhibition of Human Complement Factor H and Secretory IgA Binding via PspC

ABSTRACT Pneumococcal surface protein C (PspC) is an important candidate for a cost-effective vaccine with broad coverage against pneumococcal diseases. Previous studies have shown that Streptococcus pneumoniae is able to bind to both human factor H (FH), an inhibitor of complement alternative pathway, and human secretory IgA (sIgA) via PspC. PspC was classified into 11 groups based on variations of the gene. In this work, we used three PspC fragments from different groups (PspC3, PspC5, and PspC8) to immunize mice for the production of antibodies. Immunization with PspC3 induced antibodies that recognized the majority of the clinical isolates as analyzed by Western blotting of whole-cell extracts and flow cytometry of intact bacteria, while anti-PspC5 antibodies showed cross-reactivity with the paralogue pneumococcal surface protein A (PspA), and anti-PspC8 antibodies reacted only with the PspC8-expressing strain. Most of the isolates tested showed strong binding to FH and weaker interaction with sIgA. Preincubation with anti-PspC3 and anti-PspC5 IgG led to some inhibition of binding of FH, and preincubation with anti-PspC3 partially inhibited sIgA binding in Western blotting. The analysis of intact bacteria through flow cytometry showed only a small decrease in FH binding after incubation of strain D39 with anti-PspC3 IgG, and one clinical isolate showed inhibition of sIgA binding by anti-PspC3 IgG. We conclude that although anti-PspC3 antibodies were able to recognize PspC variants from the majority of the strains tested, partial inhibition of FH and sIgA binding through anti-PspC3 antibodies in vitro could be observed for only a restricted number of isolates.

Análise das cepas de Streptococcus pneumoniae causadores de pneumonia invasiva: sorotipos e sensibilidade aos antimicrobianos

OBJECTIVES: To identify the most common pneumococcal serotypes in children hospitalized with invasive pneumonia, correlate isolated serotypes with those included in conjugate vaccines, and ascertain the sensitivity of the isolated pneumococcal strains to penicillin and other antibiotics. METHODS: From January 2003 to October 2008, a retrospective study of hospitalized children with a diagnosis of Streptococcus pneumoniae pneumonia was conducted at the university hospital of Universidade de Sao Paulo. Criteria for inclusion were: age greater than 29 days and less than 15 years, radiological and clinical diagnosis of pneumonia, and isolation of Streptococcus pneumoniae in blood cultures and/or pleural effusion. RESULTS: The study included 107 children. The most common serotypes were 14 (36.5%), 1 (16%), 5 (14.6%), 6B (6.3%) and 3 (4.2%). The proportion of identified serotypes contained in the heptavalent, 10-valent and 13-valent conjugate vaccines was 53.1, 86.5, and 96.9%, respectively. Pneumococcal strains were sensitive to penicillin (minimum inhibitory concentration, MIC 8 µg/mL) according to the Clinical and Laboratory Standards Institute 2008 standards. Tested isolates were highly sensitive to vancomycin, rifampicin, ceftriaxone, clindamycin, erythromycin, and chloramphenicol. CONCLUSIONS: Our results confirm a significant potential impact of conjugate vaccines, mainly 10-valent and 13-valent, on invasive pneumonia. Furthermore, susceptibility testing results show that penicillin is still the treatment of choice for invasive pneumonia in our setting.

Frequency of BKC-1-Producing Klebsiella Species Isolates.

ABSTRACT BKC-1 is a new class A serine carbapenemase that was recently identified in Klebsiella pneumoniae clinical isolates. The principal objective of this study was to evaluate the frequency of blaBKC-1 by testing a collection of Klebsiella isolates. Only 2 of 635 Klebsiella isolates (0.3%) carried blaBKC-1. The two BKC-1-producing isolates belonged to clonal complex 442 and possessed identical pulsed-field gel electrophoresis patterns. The blaBKC-1 gene was inserted into a 10-kb plasmid that was identical to the previously reported plasmid, p60136. The BKC-producing K. pneumoniae isolates presented also possessed other mechanisms for beta-lactam resistance, such as genes encoding extended-spectrum beta-lactamases and mutations in the genes ompK35 and ompK36, encoding the major porins.

SUSCEPTIBILITY TO ANTIBIOTICS IN URINARY TRACT INFECTIONS IN A SECONDARY CARE SETTING FROM 2005-2006 AND 2010-2011, IN SÃO PAULO, BRAZIL: DATA FROM 11,943 URINE CULTURES

Introduction: Urinary tract infection (UTI) has a high incidence and recurrence, therefore, treatment is empirical in the majority of cases. Objectives: The aim of this study was to analyze the urine cultures performed at a secondary hospital, during two periods, 2005-2006 and 2010-2011, and to estimate the microbial resistance. Patients and methods: We analyzed 11,943 aerobic urine cultures according to basic demographic data and susceptibility to antibiotics in accordance with the Clinical and Laboratory Standards Institute (CLSI) for Vitek 1 and 2. Results: Most of our cohort consisted of young adult females that were seen at the Emergency Department. E. coli was the most frequent (70.2%) among the 75 species isolated. Resistance of all isolates was ≥ 20% for trimethoprim/sulfamethoxazole (TMP/SMX), norfloxacin, nitrofurantoin, cefazolin and nalidixic acid. Although E. coli was more susceptible (resistance ≥ 20% for TMP/SMX and nalidixic acid) among all of the isolates, when classified by the number and percentage of antibiotic resistance. Global resistance to fluoroquinolones was approximately 12%. Risk factors for E. coli were female gender and an age less than 65 years. Men and patients older than 65 years of age, presented more resistant isolates. Extended spectrum beta-lactamases (ESBL) were identified in 173 out of 5,722 Gram-negative isolates (3.0%) between 2010 and 2011. Conclusion: E. coli was the most frequent microbe isolated in the urine cultures analyzed in this study. There was a significant evolution of bacterial resistance between the two periods studied. In particular, the rise of bacterial resistance to fluoroquinolones was concerning.

Características do transplante cardíaco neonatal e infantil

OBJECTIVE: Relate the characteristics of the heart transplantation in children with complex congenital heart diseases and severe cardiomyopathies. The present article was written to show the three year experience of this procedure at the Instituto do Coracao HC-FMUSP. METHODS: The methodology used was based on surgical procedure in congenital heart disease, heart transplant indication criteria, inclusion criteria for donors, postoperative management, immunosupression and prophylaxis as well as treatment for potential complications. RESULTS: From November 1992 to June 1996, fourteen children, aged 12 days old to six years of age (mean: 2.2 years), underwent transplantation. Fifty-seven percent of recipients were male; weight ranged from 3.5 to 17.8 kg (mean: 10.3 kg). The mean age of donors was 4.4 years (a range of three weeks to ten years), 80% male, weight ranging from 3.8 to 20 kg (median 14.3 kg). The survival rate was 85.7% (two deaths in 14 patients). The follow-up was between one month to three years (average 16 months). The most important complications were systemic hypertension, acute rejection and infection. The number of rejections and infections per patient were 3.5 and 3.3 episodes respectively. CONCLUSIONS: In this experience heart transplantation has been giving a chance for children with complex congenital heart diseases and cardiomyopathies, with a survival rate of 85.7%.

Influence of nitrendipine and verapamil on plasma levels, urinary excretion, and beta-blocking effect of metoprolol

SummaryFollowing randomized allocation eight healthy volunteers were treated for 1 week each with metoprolol alone (100 mg twice daily), verapamil 80 mg three times a day plus metoprolol 100 mg twice daily, and with nitrendipine 20 mg twice daily. Plasma levels and urinary recovery of the beta-blocker, antipyrine clearance, and heart rate on exercise were measured. Verapamil and nitrendipine slightly prolonged elimination half-life of metoprolol. The urinary recovery of the parent beta-blocker and of its α-hydroxy metabolite was elevated by both calcium antagonists (verapamil and nitrendipine). Exercise tachycardia (150 beats/min without drugs) was inhibited more pronounced on the combination therapies than under metoprolol administration alone. Results of the present study indicate that calcium antagonists enhance inhibition of exercise tachycardia caused by metoprolol, possibly due to their binding to myocardial beta-adrenergic receptors which is known from the literature. As both calcium antagonists did not increase plasma levels of metoprolol, in the present study a kinetic interaction between the beta-blocker and the calcium channel blockers investigated does not appear to be responsible for the pharmacodynamic effects observed.