Role of joint aspiration before re-implantation in patients with a cement spacer in place.

BACKGROUND: The usefulness of a mandatory joint aspiration before re-implantation in patients with a cement spacer already in place is unclear. AIM: To evaluate the role of culturing synovial fluid obtained by joint aspiration before re-implantation in patients who underwent a two-stage septic revision. METHODS: A retrospective observational study was conducted, including patients that underwent a two-stage septic revision (hip or knee) from 2010 to 2017. After the first stage revision and according to intraoperative culture results, all patients were treated with an antibiotic protocol for 6-8 wk. Following 2 wk without antibiotics, a culture of synovial fluid was obtained. The results of these cultures were recorded and compared with cultures obtained during re-implantation surgery. RESULTS: Forty-one patients (20 hip and 21 knee spacers) were included in the final analysis. In 39 cases, the culture of synovial fluid was negative, while in the remaining 2 cases (knee spacers) no analysis was possible due to dry tap. In 5 of the patients, two or more intraoperative cultures taken during the re-implantation surgery were positive. CONCLUSION: We found no evidence to support mandatory joint aspiration before re-implantation in patients with a cement spacer in place.

Role of bacterial colonisation of vancomycin-gentamicin spacers in two-stage arthroplasty revision surgery: the usefulness of spacer sonication.

PURPOSE: In two-stage replacements for septic loosening, some studies have suggested an association between bacterial colonisation of spacers and a higher number of complications after implantation of the definitive prosthesis. Our study aimed to determine the reoperation rate of patients undergoing two-stage revision surgery according to the culture results of spacer sonication. METHODS: A retrospective observational study was conducted in which hip or knee spacers implanted at our institution with a diagnosis of periprosthetic joint infection from 2010 to 2018 were analysed. Patients were grouped into three categories: A. Patients with positive spacer sonication fluid culture, with or without positive cultures of the rest of the samples. B. Patients with negative spacer sonication culture and negative cultures of the rest of intraoperative samples. C. Patients with negative spacer sonication culture but positive cultures of the rest of intraoperative samples. RESULTS: A total of 45 spacers were analysed: 10 were included in group A, 24 in group B and 11 in group C. The reoperation rate during the first year after the 2-stage revision surgery was 20%, 29.2% and 54.5% for each group, respectively, due to an infection in 10%, 20.8% and 45.5%. Spacers were colonised in all cases by low virulent micro-organisms. CONCLUSION: In our study, bacterial colonisation of the spacer is not associated with a higher rate of reoperation. The group of patients with positive intraoperative cultures during the second-stage had the highest reoperation rate.

Higher accuracy of genotypic identification compared to phenotyping in the diagnosis of coagulase-negative staphylococcus infection in orthopedic surgery.

PURPOSE: To determine whether Repetitive Extragenic Palindromic PCR (rep-PCR) genotyping can improve the diagnosis of coagulase-negative staphylococcal (CoNS) orthopaedic infections in comparison to phenotyping. METHODS: Prospective study comparing the results of phenotypic/genotypic (rep-PCR) testing in patients with suspected CoNS infection. Each strain was analysed using both methods. Strains identified as identical in ≥2 samples were considered as pathogenic. RESULTS: 255 CoNS strains from 52 surgical episodes were included. Infection was diagnosed by phenotyping in 38(73%) cases and by genotyping in 40(77%). The Kappa index was 0.59. Sensitivity, Specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) for phenotyping (vs. rep-PCR) were: 88%, 75%, 92%, and 64%. 5/14(36%) of cases not considered as true infections by phenotyping were diagnosed as infections with genotyping. In a subgroup of 203 strains from 41 surgical procedures with orthopaedic implants, the kappa index was 0.68. Sensitivity, Specificity, PPV, and NPV for phenotyping were: 93%, 73%, 90% and 80%. Again, 2/10 episodes in which CoNS were considered non-infective by phenotyping were diagnosed as infected by genotyping. CONCLUSIONS: Rep-PCR genotyping can identify identical CoNS strains that differ in their phenotype and should be used as a complementary technique. One-third of infected cases may be misdiagnosed without genotypic analysis.

Relationship between skin and urine colonization and surgical site infection in the proximal femur fracture: a prospective study.

PURPOSE: Antibiotic prophylaxis is routinely used in the surgical management of proximal femur fractures. The role of bacterial colonization of the skin and urine in the development of deep surgical site infections (SSI) is yet to be elucidated. This study aimed to evaluate the role of previous skin and urine colonization in the development of deep SSI after a proximal femoral fracture surgery. METHODS: We conducted a prospective observational study in 326 patients > 64 years old, who were scheduled to surgery. Cultures from skin samples of the surgical site and from urine were performed prior to the procedure, and cefazoline was administered as prophylaxis. RESULTS: Skin microbiota was isolated in 233 (71.5%) cases; 8 (2.5%) samples were positive for other bacteria, and 85 (26%) were negative. Of 236 urine samples, 168 were negative or contaminated (71.2%), and 68 (28.8%) were positive, being 58/236 for Enterobacterales (24.6%). Acute deep SSI were diagnosed in nine out of 326 patients (2.7%), and two (22%) were infected by Gram-negative bacilli. Of the 9 cases, normal skin microbiota was isolated in 7 (78%), and the remaining two were negative. Seven cases had negative or contaminated urine cultures, and the one with E. coli did not correlate with SSI bacteria. CONCLUSION: In our elderly hip fracture population, most patients harbored normal skin microbiota, and Enterobacterales urine cultures were positive in one-quarter of cases. There was no relationship between skin colonization, urine culture, and deep SSI. We therefore do not believe that our patients would benefit from modifying the current antibiotic prophylaxis.

Periprosthetic joint infection by Propionibacterium acnes: Clinical differences between monomicrobial versus polymicrobial infection.

OBJECTIVE: To compare a series of monomicrobial Propionibacterium acnes (P. acnes) knee and hip periprosthetic joint infection (PJI) cases with cases of polymicrobial PJI which included P. acnes. We hypothesized that the presence of a polymicrobial P. acnes infection would lead to worse outcomes than those in cases of monomicrobial P. acnes PJI. METHODS: Retrospective multicentre study. All patients with hip or knee PJIs including P. acnes diagnosed from August-2002 to July-2013 in two university hospitals were included. We collected demographic data, McPherson classification, local signs of infection (swelling or wound drainage), laboratory and histological data, surgical management, antibiotic treatment and outcomes. Data were compared between two groups: cases of monomicrobial P. acnes PJI, and cases of polymicrobial PJI involving P. acnes. RESULTS: Thirty-eight patients who presented with 38 PJIs were included; median age was 71 (IQR:62.5-79); 21 were men (55%); median follow-up was 42 months (IQR:17.5-58). Local signs of infection were present in 14 patients (36.8%); ESR>30 mm/h in 14 patients (36.8%); CRP>1 mg/dl in 15 patients (39.5%); 11 out of 25 patients (44%) had positive preoperative cultures from joint aspiration. Positive histologic studies (Feldman's criteria) were found in 5 out of 28 patients (17.8%). Twenty-four patients (63%) had monomicrobial PJIs; 14 patients (37%) had polymicrobial PJIs. There were no significant outcome differences between monomicrobial and polymicrobial PJIs cases; overall, the success rates were 79.2% and 85.7% respectively (P > 0.05). CONCLUSIONS: We did not find any significant differences between monomicrobial and polymicrobial P. acnes PJI outcomes. ESR, CRP and histologic study are established parameters for diagnosing PJI which did not prove useful in P. acnes PJI.

Utilidad del Quantiferon-TB Gold in Tube en el cribado de la infección latente tuberculosa en personal sanitario / Usefulness of Quantiferon-TB Gold in Tube in screening for latent tuberculosis infection in health workers

INTRODUCCIÓN: El personal sanitario se considera un colectivo de riesgo por estar más expuesto a la enfermedad tuberculosa. La prueba de la tuberculina (PT) presenta el inconveniente del alto número de falsos positivos, sobre todo en pacientes vacunados con BCG. En los últimos años las técnicas denominadas IGRAS parecen mejorar estos inconvenientes, si bien plantean otros dilemas. Nuestro objetivo es analizar la concordancia de ambos test y realizar un estudio de coste-beneficio de las posibles estrategias diagnósticas. MATERIAL Y MÉTODOS: Entre enero de 2010 y octubre de 2011 se estudió todo el personal sanitario del Hospital Universitari Mútua Terrassa de nueva incorporación y aquellos que tenían su revisión laboral. También se estudiaron trabajadores que habían sido contactos de pacientes ingresados con tuberculosis, sin aislamiento inicial. En todos los casos se realizó la PT y paralelamente un Quantiferon-TB Gold in Tube® (QF-G-IT) en sangre. Se consideró positiva una PT ≥ 10 mm y un QF-G-IT > 0,35 IU/ml. Se descartó enfermedad tuberculosa en todos los profesionales mediante radiología de tórax. Se hizo un estudio de coste beneficio de 3 estrategias posibles de estudio de la infección latente tuberculosa (ILT). RESULTADOS: Se estudiaron 226 profesionales sanitarios, con una media de edad de 30,65 ± 16 años. Cuarenta y cuatro (19,4%) presentaban vacuna con BCG, y en 8 (3,5%) se desconocía. La PT fue positiva en 33 (14,6%) casos y el QF-G-IT en 17 (7,5%). En 15 casos ambos valores de la PT y del QF-G-IT fueron positivos y coincidentes. En 18 (8%) profesionales la PT fue positiva, con un valor de QF-G-IT negativo. La concordancia entre ambas pruebas fue del 91%, con un kappa de 0,55. En vacunados, la concordancia fue del 70,5%, con un kappa de 0,33, mientras que en no vacunados fue del 98,9%, con un kappa de 0,65. La estrategia de cribado de la ILT más económica fue la basada en la PT, pero seguida muy de cerca por la estrategia basada en la PT con reconfirmación de los positivos con QF-G-IT, que fue la que mostró un mejor coste-beneficio ya que reduce profilaxis innecesarias. CONCLUSIONES: El QF-G-IT parece ser una técnica adecuada en la detección de la ILT y permite detectar los falsos positivos de la PT debidos a la vacuna con BCG. En este colectivo el QF-G-IT podría ser la prueba idónea para detectar a los realmente infectados y evitar así quimioprofilaxis innecesarias. La estrategia que mostró ser más coste-beneficio fue la basada en la PT con reconfirmación de los casos positivos mediante QF-G-IT

INTRODUCTION: Healthcare workers (HW) are considered a risk group for exposure to tuberculosis. Screening for latent tuberculosis infection (LTBI) is mandatory in all HW. The Tuberculin test (TT) has been used up until now for LTBI screening, but gives a high number of false positives, especially in patients vaccinated with BCG. Diagnostic methods based on detection of specific gamma interferon (IGRA) have recently appeared on the market in order to improve these drawbacks, but pose other dilemmas. The aim of this study is to determine the agreement between the two types of test and to carry out a cost-benefit study of the possible diagnostic strategies. MATERIAL AND METHODS: All newly hired HW by the Hospital Universitari Mútua Terrassa between January 2010 and October 2011 we were included in the study, as well as those who had their occupational review. Workers who been in contact with patients admitted with tuberculosis before the initial isolation were also tested. In all cases a parallel TT and serum QuantiFeron-TB Gold-in-Tube® (QF-G-IT) assays were performed. TB disease was ruled out in all professional by chest X-ray. The TT was considered positive when it was equal to or more than 10 mm and if the QF-G-IT was 0.35 IU/mL. A cost-effectiveness analysis was designed with three possible strategies to detect LTBI in order to find the one with the best cost-benefit. RESULTS: A total of 226 HW were studied, with a mean age 30.65 ± 16, of whom 44 (19.4%) had previous BCG vaccination history, and 8 (3.5%) unknown. The TT was positive in 33 (14.6%) cases and the QF-G-IT in 17 (7.5%). The values of the TT and QF-G-IT were both positive in 15 cases. In 18 (8%) The TT was positive in 18 (8%) of cases with a negative QF-G-IT value. The agreement between the two tests was 91%, with a Kappa of 0.55. In vaccinated cases, the correlation was 70.5%, with a Kappa of 0.33, while in unvaccinated it was 98.9% with a Kappa of 0.65. The cheapest screening strategies for LTBI diagnosis were hose based on TT, but followed closely by the strategy based on TT with reconfirmation of positives with QF-G-IT. CONCLUSIONS: QF-G-IT seems to be a very sensitive technique to detect LTBI and allows false positives due to TT to be detected, particularly in BCG vaccinated HW. In this group QF-G-IT could be the ideal test to detect truly infected staff, and avoid unnecessary chemoprophylaxis. The most cost-benefit strategy was those based in TT with reconfirmation or rejection of positive cases by QF-G-IT

[Usefulness of Quantiferon-TB Gold in Tube® in screening for latent tuberculosis infection in health workers]. / Utilidad del Quantiferon-TB Gold in Tube(®) en el cribado de la infección latente tuberculosa en personal sanitario.

INTRODUCTION: Healthcare workers (HW) are considered a risk group for exposure to tuberculosis. Screening for latent tuberculosis infection (LTBI) is mandatory in all HW. The Tuberculin test (TT) has been used up until now for LTBI screening, but gives a high number of false positives, especially in patients vaccinated with BCG. Diagnostic methods based on detection of specific gamma interferon (IGRA) have recently appeared on the market in order to improve these drawbacks, but pose other dilemmas. The aim of this study is to determine the agreement between the two types of test and to carry out a cost-benefit study of the possible diagnostic strategies. MATERIAL AND METHODS: All newly hired HW by the Hospital Universitari Mútua Terrassa between January 2010 and October 2011 we were included in the study, as well as those who had their occupational review. Workers who been in contact with patients admitted with tuberculosis before the initial isolation were also tested. In all cases a parallel TT and serum QuantiFeron-TB Gold-in-Tube(®) (QF-G-IT) assays were performed. TB disease was ruled out in all professional by chest X-ray. The TT was considered positive when it was equal to or more than 10mm and if the QF-G-IT was 0.35 IU/mL. A cost-effectiveness analysis was designed with three possible strategies to detect LTBI in order to find the one with the best cost-benefit. RESULTS: A total of 226 HW were studied, with a mean age 30.65 ± 16, of whom 44 (19.4%) had previous BCG vaccination history, and 8 (3.5%) unknown. The TT was positive in 33 (14.6%) cases and the QF-G-IT in 17 (7.5%). The values of the TT and QF-G-IT were both positive in 15 cases. In 18 (8%) The TT was positive in 18 (8%) of cases with a negative QF-G-IT value. The agreement between the two tests was 91%, with a Kappa of 0.55. In vaccinated cases, the correlation was 70.5%, with a Kappa of 0.33, while in unvaccinated it was 98.9% with a Kappa of 0.65. The cheapest screening strategies for LTBI diagnosis were those based on TT, but followed closely by the strategy based on TT with reconfirmation of positives with QF-G-IT. CONCLUSIONS: QF-G-IT seems to be a very sensitive technique to detect LTBI and allows false positives due to TT to be detected, particularly in BCG vaccinated HW. In this group QF-G-IT could be the ideal test to detect truly infected staff, and avoid unnecessary chemoprophylaxis. The most cost-benefit strategy was those based in TT with reconfirmation or rejection of positive cases by QF-G-IT.

Pseudomonas aeruginosa and mortality after hospital admission for chronic obstructive pulmonary disease.

BACKGROUND: Pseudomonas aeruginosa (PA) is isolated in advanced stages of chronic obstructive pulmonary disease (COPD). OBJECTIVES: The aim of our study was to determine whether PA isolation during hospitalization for COPD exacerbation was associated with a poorer prognosis after discharge. METHODS: We prospectively studied all patients with COPD exacerbation admitted between June 2003 and September 2004. A sputum culture was obtained at admission. Comorbidity, functional dependence, hospitalizations during the previous year, dyspnea, quality of life and other variables previously associated with mortality in COPD were studied. Spirometry and a 6-min walking test were performed 1 month after discharge. Mortality was evaluated 3 years after discharge. RESULTS: A total of 181 patients were included in the study. Of these, 29 (16%) had PA in the sputum. The mean age was 72 years, and mean basal postbronchodilator forced expiratory volume in 1 s was 45.2% predicted (SD 14.4). The mean point value on the BODE index was 5.1 (SD 2.5). At 3 years, 17 of 29 patients (58.6%) in the PA group had died, compared to 53 of the 152 non-PA patients [34.9%; p < 0.004; hazard ratio (HR) 2.23, 95% confidence interval (CI) 1.29-3.86]. In the multivariate analysis, PA remained statistically related to posthospital mortality (p = 0.02; HR 2.2, 95% CI 1.2-4.2) after adjustment for age (p < 0.02; HR 1.04, 95% CI 1.007-1.07), BODE index (p < 0.02; HR 1.15, 95% CI 1.02-1.3) and comorbidity (p < 0.02; HR 1.24, 95% CI 1.03-1.5). CONCLUSIONS: PA isolation in sputum in patients hospitalized for acute exacerbation of COPD is a prognostic marker of 3-year mortality. Poor prognosis is independent of other significant predictors of mortality such as BODE index, age and comorbidity, as measured by the Charlson index.

Diagnosis of tuberculosis infection by tuberculin skin test and a whole-blood interferon-γ release assay in patients considered for anti-tumor necrosis factor-α therapy.

To assess the performance of QuantiFERON®-TB Gold in-Tube (QFT-GIT; Cellestis, Carnegie, Australia) and tuberculin skin test (TST) in patients with immune-mediated inflammatory diseases (IMID), before anti-tumor necrosis factor-α (TNF-α) therapy, and to compare the results with those from the healthy population. Three hundred fourteen subjects (214 with IMID and 100 controls) underwent simultaneous QFT-GIT and TST. QFT-GIT was positive in 21% of IMID patients and in 16% of controls (P = 0.29). Among IMID patients, 21% tested positive by QFT-GIT and 24%, by TST (P = 0.30). Positive QFT-GIT results were not affected by immunosuppressive therapy (odds ratio, 0.78; 95% confidence interval [CI], 0.36-1.68; P = 0.52). Agreement between both tests in those patients who tested positive by one of the tests was 50% (95% CI, 37.2-62.8). QFT-GIT is useful for identifying IMID patients requiring treatment of latent tuberculosis before anti-TNF therapy. However, given the poor agreement between TST and QFT-GIT, we advocate a strategy of simultaneous testing to optimize diagnostic sensitivity.

Procalcitonin levels are lower in intensive care unit patients with H1N1 influenza A virus pneumonia than in those with community-acquired bacterial pneumonia. A pilot study.

PURPOSE: The purpose of the study was to know the kinetics of procalcitonin (PCT), C-reactive protein (CRP), and white blood cell (WBC) in critically ill patients with H1N1 influenza A virus pneumonia and to compare levels of these inflammatory mediators with patients with acute community-acquired bacterial pneumonia. MATERIALS AND METHODS: An observational study in a mixed intensive care unit (ICU) at a general university hospital was performed. All consecutive patients admitted to the ICU with a diagnosis of severe acute community-acquired pneumonia from September 2009 to December 2009 were included. Viral (H1N1 influenza A) and bacterial microbiological diagnoses were done in every patient. At admission, demographics, comorbidities, Simplified Acute Physiology Score, Sequential Organ Failure Assessment, Lung Injury Score, and Pao(2)/Fio(2) were recorded. At admission and after 24, 48, and 120 hours, WBC, CRP, and PCT levels were obtained. Finally, hospital and ICU length of stay and mortality were recorded. RESULTS: No differences in CRP or WBC were found between H1N1-positive patients and H1N1-negative patients (patients with acute community-acquired bacterial pneumonia). Procalcitonin levels at admission were lower in H1N1-positive patients (PCT = 0.4 [0.1-6.1] ng/mL) than in the H1N1-negative patients (24.8 [13.1-34.5] ng/mL). Procalcitonin significantly decreased with time but remained lower in the H1N1-positive group at all measurements (P < .05 for all comparisons). CONCLUSIONS: Among patients admitted to the ICU with pneumonia, the PCT level could help identify H1N1 influenza A virus pneumonia and thus enable earlier antiviral therapy.

IFN-γ response on T-cell based assays in HIV-infected patients for detection of tuberculosis infection.

BACKGROUND: Individuals infected with human immunodeficiency virus (HIV) have an increased risk of progression to active tuberculosis following Mycobacterium tuberculosis infection. The objective of the study was to determine IFN-γ responses for the detection of latent tuberculosis infection (LTBI) with QuantiFERON-TB GOLD In Tube (QFT-G-IT) and T-SPOT.TB in HIV patients, and evaluate the influence of CD4 cell count on tests performance. METHODS: We studied 75 HIV patients enrolled for ongoing studies of LTBI with T-SPOT.TB, QFN-G-IT and TST. Mean CD4 cell counts ± standard deviation was 461.29 ± 307.49 cells/µl. Eight patients had a BCG scar. RESULTS: T-SPOT.TB, QFN-G-IT and TST were positive in 7 (9.3%), 5 (6.7%) and 9 (12%) cases, respectively. Global agreement between QFN-G-IT and T-SPOT.TB was 89% (κ = 0.275). The overall agreement of T-SPOT.TB and QFN-G-IT with TST was 80.8% (κ = 0.019) and 89% (κ = 0.373), respectively. We have found negative IFN-γ assays results among 2 BCG-vaccinated HIV-infected individuals with a positive TST. In non BCG-vaccinated patients, QFN-G-IT and TST were positive in 5 cases (7.5%) and T-SPOT.TB in 7 (10.4%). In contrast, in BCG-vaccinated patients, only TST was positive in 4/8 (50%) of the cases. The differences obtained in the number of positive results between TST and both IFN-γ assays in BCG vaccinated patients were significant (95% CI 3-97%, p = 0.046), however, the confidence interval is very wide given the small number of patients. In patients with CD4< 200, we obtained only one (5%) positive result with T-SPOT.TB; however, QFN-G-IT and TST were negative in all cases. On the contrary, percentages of positive results in patients with CD4> 200 were 10.9% (6/55), 9.1% (5/55) and 16.4% (9/55) with T-SPOT.TB, QFN-G-IT and TST, respectively. CONCLUSIONS: IFN-γ tests have the benefit over TST that are less influenced by BCG vaccination, consequently they are more specific than TST. Although our number of patients with advance immunosuppression is limited, our study suggests that IFN-γ assays are influenced with level of immunosuppression. The use of IFN-γ assays could be a helpful method for diagnosing LTBI in HIV population.

Mortality of tuberculosis in very old people.

OBJECTIVES: To describe the clinical characteristics and outcomes of tuberculosis (TB) in elderly people. DESIGN: Observational analysis of a prospective cohort of adults with TB (1995-2004). A case-control study to determine attributable mortality to TB in very old people was done. RESULTS: Of 319 patients with TB, 109 (34.2%) were aged 65 and older. The older group was more likely to have comorbidities (1.4% vs 0.4%; P<.001), extrapulmonary and disseminated TB (50.4% vs 26.1%; P<.001), toxicity (22% vs 9.8%; P=.006), and 30-day mortality (18.3% vs 1.6%; P<.001). When patients aged 65 to 79 were compared with those aged 80 and older, only differences in TB-related mortality were detected (9.8% vs 44.4%; P=.01). In the attributable mortality analysis, 30-day and 6-month mortality were higher in very old patients with TB than in controls without TB (41.7% vs 11.1%, P=.005; 45.8% and 19.4%, P=.01, respectively). No differences in mortality were shown when excluding patients with postmortem TB diagnosis or those who died within the first 72 hours of diagnosis. CONCLUSION: Older people with TB had a higher frequency of atypical features, more adverse drug reactions, and greater TB-related mortality than younger people. Data suggest that very old patients with TB have higher mortality, but if diagnosed early and adequately treated, very old patients with TB do not have greater mortality than those without.

Impact of amoxicillin, associated or not with clavulanic acid, on pharyngeal colonization and selection of Streptococcus pneumoniae resistance in children under 5 years of age.

Among young children, pneumococcal nasopharyngeal colonization (NPC) rates of >90% have been described. The aim of our study was to assess the effect of amoxicillin exposure on the NPC. From Dec 2001 to Feb 2004, less than 5 years old children with respiratory symptoms and fever who were prescribed amoxicillin were eligible. Three nasopharyngeal swabs were taken: at the time of the initial visit (IV), 60 hours after amoxicillin discontinuation (end of treatment visit, ETV), and 4 weeks later (follow-up visit, FUV). One hundred and thirty four children were included. NPC was detected in 58.5%, 42.9% and 51% of <1, 1-2 and >2 years-old children respectively (NS). Vaccine serotypes (VS) or vaccine-related serotypes (VRS) were identified in 80%, 40% and 55% of <1-year-old, 1-2 year-old and >2-year-old children respectively (NS). The proportion of PNSSP was 60% in <1-year-old children, 43% in 1-2 year-old children and 40% in >2-year-old children (NS). 49 out of 134 (36.5%) children completed the three study visits. 51%, 22.4% and 46.9% of those were colonized at IV, ETV and FUV, respectively (p=0.007). The percentage of resistant SP was 28%, 45.5% and 8.7% (p=0.05) for penicillin. In children <1 year of age, a higher proportion of SP colonization, presence of VS and PNSSP was found. A downfall of NPC at the end of therapy was observed. NPC returned to baseline levels thanks to "de novo" colonization in half of the cases, a few weeks after.