Pneumococcal serotypes in children, clinical presentation and antimicrobial susceptibility in the PCV13 era.

The aim was to analyse invasive pneumococcal disease (IPD) serotypes in children aged ⩽17 years according to clinical presentation and antimicrobial susceptibility. We conducted a prospective study (January 2012-June 2016). IPD cases were diagnosed by culture and/or real-time polymerase chain reaction (PCR). Demographic, microbiological and clinical data were analysed. Associations were assessed using the odds ratio (OR) and 95% confidence intervals (CI). Of the 253 cases, 34.4% were aged <2 years, 38.7% 2-4 years and 26.9% 5-17 years. Over 64% were 13-valent pneumococcal conjugate vaccine (PCV13) serotypes. 48% of the cases were diagnosed only by real-time PCR. Serotypes 3 and 1 were associated with complicated pneumonia (P < 0.05) and non-PCV13 serotypes with meningitis (OR 7.32, 95% CI 2.33-22.99) and occult bacteraemia (OR 3.6, 95% CI 1.56-8.76). Serotype 19A was more frequent in children aged <2 years and serotypes 3 and 1 in children aged 2-4 years and 5-17 years, respectively. 36.1% of cases were not susceptible to penicillin and 16.4% were also non-susceptible to cefotaxime. Serotypes 14, 24F and 23B were associated with non-susceptibility to penicillin (P < 0.05) and serotypes 11, 14 and 19A to cefotaxime (P < 0.05). Serotype 19A showed resistance to penicillin (P = 0.002). In conclusion, PCV13 serotypes were most frequent in children aged ⩽17 years, mainly serotypes 3, 1 and 19A. Non-PCV13 serotypes were associated with meningitis and occult bacteraemia and PCV13 serotypes with pneumonia. Non-susceptibility to antibiotics of non-PCV13 serotypes should be monitored.

Impact of prior pneumococcal vaccination on clinical outcomes in HIV-infected adult patients hospitalized with invasive pneumococcal disease.

BACKGROUND: Recent studies in hospitalized patients with community-acquired pneumonia have found a lower risk of bacteraemia and better clinical outcomes in patients who had previously received the 23-valent pneumococcal polysaccharide vaccine (PPV) in comparison with unvaccinated individuals. The aim of this study was to assess the influence of prior PPV on clinical outcomes in HIV-infected adult patients hospitalized with invasive pneumococcal disease (IPD). METHODS: This was an observational study of all consecutive HIV-infected adults hospitalized with IPD from January 1996 to October 2007 in three hospitals in Spain. Baseline characteristics and clinical outcome-related variables were compared according to prior PPV vaccination status. RESULTS: A total of 162 episodes of IPD were studied. In 23 of these (14.2%), patients had previously received PPV. In both vaccinated and unvaccinated patients, most of the causal serotypes were included in the 23-valent PPV (76.9% and 84.1%, respectively). Overall, 25 patients (15.4%) died during hospitalization, 21 patients (13%) required admission to an intensive care unit (ICU) and 34 patients (21%) reached the composite outcome of death and/or admission to the ICU. None of the 23 patients who had previously received PPV died or required ICU admission, in comparison with 25 (18%; P=0.026) and 21 (15.1%; P=0.046), respectively, of the unvaccinated patients. The length of hospital stay for vaccinated patients was significantly shorter (8.48 vs. 13.27 days; P=0.011). CONCLUSIONS: Although 23-valent PPV failed to prevent IPD in some HIV-infected patients, vaccination produced beneficial effects on clinical outcomes by decreasing illness severity and mortality related to IPD.

Impact of early central venous catheter removal on outcome in patients with candidaemia.

Removal of central venous catheters (CVCs) from candidaemic patients is considered the reference standard of care, although this practice is not always possible. The impact of prompt catheter removal on outcome was investigated by analysing data from an active population-based surveillance study in Barcelona, Spain. Patients with candidaemia and a CVC were identified between January 2002 and December 2003. Cases with CVC removal within 2 days were classified as having early CVC removal. Outcome, defined as in-hospital mortality 2-30 days after diagnosis of candidaemia, was determined among hospitalised adults using univariate, Kaplan-Meier and multivariate logistic regression analysis. Outpatients, paediatric patients and those who died or were discharged within 2 days were excluded. The study identified 265 patients with candidaemia and a CVC. Median time from diagnosis of candidaemia to catheter removal was 1 day (range 0-29 days). Overall, 172 patients met the criteria for inclusion in the outcome study. Patients with early CVC removal differed significantly from those with delayed CVC removal. According to univariate, Kaplan-Meier and multivariate analysis, the marker most predictive of in-hospital mortality among candidaemic patients with CVCs was severity of illness. These data suggest that timing of CVC removal may best be determined after carefully considering the risks and benefits to individual patients.

Incidence and risk factors of recurrent episodes of bacteremia in adults.

BACKGROUND: Bacteremia is a cause of high morbidity and mortality. Recurrent episodes of bacteremia, its risk factors and characteristics, have been poorly evaluated in the literature, although its occurrence has been established. PATIENTS AND METHODS: Analysis of 1426 patients who presented with 1579 episodes of bacteremia and who were prospectively evaluated in a university-affiliated hospital during a 48-month period. The risk factors for a patient to develop a recurrence of bacteremia was assessed comparing those with recurrent episodes with those who survived an episode of bacteremia with no recurrence during the follow-up period. RESULTS: A total of 105 patients presented with 248 episodes of bacteremia, of which 143 episodes were recurrent (recurrence rate, 9% of all bacteremic episodes). Two factors were independently predictive of recurrent bacteremia: (1) the presence of an underlying disease (especially a rapidly fatal one [odds ratio, 7.27]) or (2) any complication during the initial episode of bacteremia. Using these factors, the prediction model was significant, but misclassification was high, with a sensitivity of 61% and a specificity of 67% for a cutoff point that maximized both factors. CONCLUSIONS: We identified risk factors for patients who presented with an initial episode of bacteremia to develop a recurrence rate. The recurrence risk factors may be used as a form of guidance for extreme preventive measures, but these factors could not predict recurrence with a high degree of accuracy.

Late prosthetic valve endocarditis. Immediate and long-term prognosis.

From 1975 to 1989, 307 consecutive episodes of infective endocarditis were diagnosed in our hospital. Of those, 35 were cases of late prosthetic valve endocarditis, defined as those occurring after 12 months of valvular replacement. Blood cultures grew streptococci in 15 patients (43 percent), staphylococci in seven (20 percent), enterococci in five (14 percent), Gram-negative bacilli of HACEK group in four (11.5 percent), and Candida in one. Blood cultures were negative in three cases (prosthetic infection was confirmed at surgery). Heart failure due to prosthetic dysfunction occurred in seven patients (20 percent) and emboli in 12 (34 percent). Early valvular replacement was performed in six patients (17 percent). Complications and mortality were dependent on the infective agent. Overall mortality was 23 percent, no death occurred from streptococcal infection, whereas mortality with endocarditis by organisms of the HACEK group and Staphylococcus was 50 percent and 43 percent, respectively. During a mean follow-up of five years, 11 patients (those with prosthetic leaks diagnosed during the active infection and patients with biologic prostheses) required surgery. There was one relapse in a patient with staphylococcal endocarditis and one recurrence, six years after the initial episode. We conclude that immediate prognosis of late prosthetic valve endocarditis depends on the infective agent. Although the immediate prognosis of streptococcal infections is good, the need for early reoperation during follow-up due to progressive perivalvular leak is high. Also, it appears that deterioration of bioprostheses proceeds swiftly after the cure of infection.

[Evolution of perinatal Escherichia coli disease in the era of group B Streptococcus prophylaxis]. / Evolución de la sepsis perinatal por Escherichia coli en la era de la profilaxis del estreptococo del grupo B.

BACKGROUND: The aim of this study was to characterize perinatal Escherichia coli disease, and to analyze its possible correlation with the employment of prophylaxis for group B streptococcal (GBS)disease. PATIENTS AND METHOD: Between 1994 and 2000, 24 neonates born in our hospital were diagnosed of early-onset E. coli disease: 12 born to mothers who received prenatal care in our center and 12 born to mothers who were referred from other hospitals shortly before labor. Three further neonates born in other centers were also referred with the same diagnosis. RESULTS: The annual rate did not change significantly (RR:1.065; confidence interval [CI] 95% -0.873-1.301; p = 0.533):from 0.6 per 1,000 live births in 1994 to 1.7 per 1,000 in 1997 and 0.5 in 2000. Among mothers, 92% presented obstetric risk factors including 68% with prematurity (mean 32.9 gestation weeks, median 32), 64% with prolonged rupture of membranes (mean 184 hours,median 44), and 56% with intrapartum fever. Twelve percent of mothers received intrapartum ampicillin as prophylaxis against GBS and 80% received antibiotics: prophylaxis for rupture of membranes in 6 cases, treatment of urinary tract infection in 6 cases and treatment of probable chorioamnionitis in 8 cases. Ampicillin-resistant E. coli was isolated in 81% of neonates. No significant correlation was found between ampicillin resistance and prematurity(p = 0.57), rupture of membranes (p = 0.63), intrapartum fever(p = 0.24) or death (p = 0.53). CONCLUSIONS: Our results suggest that perinatal E. coli disease is not related with the employment of prophylaxis against GBS disease. Instead, it seems to be related with prematurity, prolonged gestation in premature rupture of membranes and exposure to antibiotics.

[Serologic study in patients with streptococcal infective endocarditis]. / Estudio serológico en pacientes con endocarditis infecciosa estreptocócica.

BACKGROUND: Infective endocarditis is a systemic disease in which there are a continuously antigenic stimulation of immunologic system. Streptococcus is still the most frequent cause of infective endocarditis. PATIENTS AND METHODS: We investigated the presence of antibody (AB), total and IgM by indirect immune fluorescence technique, in four groups of population: streptococcal infective endocarditis (SIE), streptococcal bacteraemia (SB), Staphylococcus aureus endocarditis, and healthy people. Antigens used were: 1) their own strain isolated from the blood of patients with SIE and SB ¿homologous AB¿, and; 2) seven species of Streptococcus: Streptococcus intermedius, Streptococcus salivarius, Streptococcus bovis, Streptococcus sanguis I, Streptococcus sanguis II, nutritional dependent streptococci and Enterococcus faecalis (heterologous AB). RESULTS: Homologous antibodies: titers > or = 1/512 were found in all patients with SIE and only in 2 with SB (sensitivity 100% and specificity 93%). IgM titer (threshold 1/32) was positive only in patients with SIE (sensitivity 75,5% and specificity 100%). The fall of the AB titer was continuous and slow, despite the good clinical evolution of patients. (AB titers were > or = 1/512 and IgM > or = 1/64 in 30% of patients 1 year later). Heterologous AB: in spite of statistically significant difference found in SIE versus the other groups, sensitivity of this test (threshold 1/256) is low, confidence interval include expected random value (50%), specificity is 88%. CONCLUSIONS: The utility of homologous AB for diagnosing infective endocarditis is demonstrated. On the contrary for heterologous AB, antigenic common fractions must be found in the different species.

Impact of prompt catheter withdrawal and adequate antimicrobial therapy on the prognosis of hospital-acquired parenteral nutrition catheter-related bacteraemia.

Catheter-related bacteraemia (CRB) is a cause of death in hospitalized patients, and parenteral nutrition (PN) is a risk factor. We aim to describe the prognosis of PN-CRB and the impact of catheter extraction within 48 h from bacteraemia. All consecutive hospitalized adult patients with CRB (2007-2012) were prospectively enrolled. Factors associated with 30-day mortality were determined by logistic regression analysis. Among 847 episodes of CRB identified, 291 (34%) episodes were associated with short-term catheter use for PN. Cure was achieved in 236 (81%) episodes, 42 (14.5%) patients died within the first 30 days, 7 (2.5%) relapsed, and 6 (2%) had re-infection. On multivariate analysis, previous immunosuppressive therapy (OR 5.62; 95% CI 1.69-18.68; p 0.0048) and patient age (OR 1.05; 95% CI 1.02-1.07; p 0.0009) were predictors of 30-day mortality, whereas catheter removal within 48 h of bacteraemia onset (OR 0.26; 95% CI 0.12-0.58; p 0.0010) and adequate empirical antibiotic treatment (OR 0.36; 95% CI 0.17-0.77; p 0.0081) were protective factors. Incidence of PN-CRB decreased from 5.36 episodes/1000 days of PN in 2007 to 2.9 in 2012, yielding a 46.1% rate reduction (95% CI 15.7-65.5%), which may be attributable to implementation of a multifaceted prevention strategy. In conclusion, short-term PN-CRB accounted for one-third of all episodes of CRB in our setting, and 14.5% of patients died within 30 days following bacteraemia. Our findings suggest that prompt catheter removal and adequate empirical antibiotic treatment could be protective factors for 30-day mortality. Concomitantly with implementation of a multifaceted prevention strategy, PN-CRB incidence was reduced by half.

Impact of the emergence of non-vaccine pneumococcal serotypes on the clinical presentation and outcome of adults with invasive pneumococcal pneumonia.

The introduction of the 7-valent pneumococcal conjugate vaccine in children has led to a change in the pattern of pneumococcal serotypes causing pneumococcal disease. The aim of this study was to compare the clinical presentation and outcome of invasive pneumococcal pneumonia (IPP) in adults between the pre and post-vaccine era. We have conducted an observational study of all adults hospitalized with IPP, from 1996 to 2001 (pre-vaccine period), and from 2005 to 2009 (post-vaccine period). Incidence, serotype distribution and clinical data were compared between both periods. A total of 653 episodes of IPP were diagnosed. The overall incidence of IPP increased from 14.2 to 17.9 cases per 100 000 population-year (p 0.003). In the post-vaccine period IPP caused by vaccine serotypes decreased (-36%; 95% CI, -52 to -15) while IPP caused by non-vaccine serotypes increased (71%; 95% CI, 41-106). IPP in the post-vaccine period was associated with higher rates of septic shock (19.1% vs. 31.1%, p <0.001). Among patients aged 50-65 years there was a trend towards a greater proportion of case-fatalities (11.6-23.5%, p 0.087). Independent risk factors for septic shock were IPP caused by serotype 3 (OR 2.38; 95% CI, 1.16-4.87) and serotype 19A (OR 6.47, 95% CI, 1.55-27). Serotype 1 was associated with a lower risk of death (OR 0.1; 95% CI, 0.01-0.78). In conclusion, the incidence of IPP in the post-vaccine period has increased in our setting, it is caused mainly by non-vaccine serotypes and it is associated with higher rates of septic shock.

Immediate and long-term outcome of left-sided infective endocarditis. A 12-year prospective study from a contemporary cohort in a referral hospital.

The aim of this study was to describe the immediate and long-term prognosis of a contemporary cohort of patients with left-sided infective endocarditis (LSIE). A prospective observational cohort study was conducted in a referral centre. Between January 2000 and December 2011, all consecutive adult patients with LSIE were followed-up until death, relapse, recurrence, need for late surgery, or last control. During the active phase of IE, 174 of 438 patients underwent surgery (40% overall; 43% native valve (NVIE), 30% prosthetic valve (PVIE)) and 125 died (29% overall; 26% NVIE, 39% PVIE). The median follow-up in survivors was 3.2 years (interquartile range (IQR) 1.0-6.0 years). Relapses occurred in seven patients (2.2%; 95% CI, 1.1-4.5) and recurrences in eight (2.6%; 95% CI, 1.3-5.0), with an incidence density of 0.0067 per patient-year (95% CI, 0.0029-0.0133) and high mortality (75% of recurrences). Only four of 130 survivors (3.1%; 95% CI, 1.2-7.6) who were treated surgically during the active phase of the disease, and 14/183 (7.7%; 95% CI, 4.6-12.4) of those not undergoing surgery needed operation during follow-up (p 0.09). In the 313 survivors, actuarial survival was 86% at 1 year (87% NVIE, 83% PVIE), 79% at 2 years (81% NVIE, 72% PVIE) and 68% at 5 years (71% NVIE, 57% PVIE). At 1 year, 115 of 397 patients (29.0%; 95% CI, 24.7-33.6) remained alive, with no surgery requirement, relapse or recurrence. LSIE is associated with considerable in-hospital and long-term mortality, especially PVIE. However, relapses, recurrences and the need for late surgery are uncommon.

[Incidence of central line-associated bloodstream infection in an intensive care unit]. / Incidencia de bacteriemia asociada a catéter venoso central en una unidad de cuidados intensivos.

BACKGROUND: Central line-associated bloodstream infection (CLABSI) is one of the most common nosocomial infections. The incidence is higher in paediatric patients than in adults, especially in those admitted to Intensive Care Units (ICU). CLABSI-related morbidity makes it a major health problem; therefore it is necessary to develop prevention strategies against it. PATIENTS AND METHODS: An intervention study in a paediatric ICU (PICU) was performed, in order to assess the impact of the introduction of the program «Bacteraemia zero¼ in December 2007. This program aims to prevent CLABSI. Demographic data and variables related to hospitalisation and infection were collected from January to December 2007 (before the intervention) and from January to December 2008 (after the intervention), and were compared. In the first period, 497 patients were studied, and 495 in the second. RESULTS: A reduction of 30.4% in the incidence of CLABSI (P=0.49) in the second year was observed (5.5 to 3.8 episodes per 1000 catheter-days). The CVC use ratio was 0.59 and 0.64, respectively. The most frequently isolated organism was coagulase-negative Staphylococcus spp. CONCLUSIONS: The implementation of a «no bacteraemia¼ program, involving all staff in the PICU as well as the professionals in infection control, reduces the incidence of CLABSI.

Prognosis of left-sided infective endocarditis in patients transferred to a tertiary-care hospital--prospective analysis of referral bias and influence of inadequate antimicrobial treatment.

The aims of this study were to compare the characteristics of adult patients with left-sided infective endocarditis (LSIE) diagnosed and treated in a tertiary-care hospital with those of patients referred from a second-level community hospital, and to establish the accuracy of diagnosis and adequacy of treatment in referred patients and the influence of this factor on outcome. A prospective observational cohort study was conducted at Hospital Universitari Vall d'Hebron, a 1000-bed teaching hospital in Barcelona (Spain) and a referral centre for cardiac surgery. One hundred and fourteen of 337 (34%) episodes of LSIE treated in our hospital occurred in transferred patients. As compared with patients diagnosed in our hospital, transferred patients acquired LSIE within the healthcare system less often (16.7% vs. 38.1%, p <0.001), were in better health (Charlson index 3 (interquartile range (IQR)) 1-4) vs. 4 (IQR 2-6), p <0.001), had more complications (94.7% vs. 78.9%, p <0.001), underwent more operations (69.3% vs. 22.1%, p <0.001), and experienced similar mortality (22.8% vs. 31.4%, p 0.100). Only 52 of 114 (45.6%) referred patients received an antimicrobial regimen included in the American, European or Spanish guidelines at the hospital of origin. After adjustment for congestive heart failure and staphylococcal infection in multivariate logistic regression, inadequate or no antimicrobial treatment at origin was a risk factor for in-hospital mortality (OR 3.3, 95% CI 1.1-10.0, p 0.030). Errors in the initial antimicrobial treatment prescribed for LSIE are associated with greater mortality.