Outpatient Parenteral Antibiotic Treatment for Infective Endocarditis: A Prospective Cohort Study From the GAMES Cohort.

BACKGROUND: Outpatient parenteral antibiotic treatment (OPAT) has proven efficacious for treating infective endocarditis (IE). However, the 2001 Infectious Diseases Society of America (IDSA) criteria for OPAT in IE are very restrictive. We aimed to compare the outcomes of OPAT with those of hospital-based antibiotic treatment (HBAT). METHODS: Retrospective analysis of data from a multicenter, prospective cohort study of 2000 consecutive IE patients in 25 Spanish hospitals (2008-2012) was performed. RESULTS: A total of 429 patients (21.5%) received OPAT, and only 21.7% fulfilled IDSA criteria. Males accounted for 70.5%, median age was 68 years (interquartile range [IQR], 56-76), and 57% had native-valve IE. The most frequent causal microorganisms were viridans group streptococci (18.6%), Staphylococcus aureus (15.6%), and coagulase-negative staphylococci (14.5%). Median length of antibiotic treatment was 42 days (IQR, 32-54), and 44% of patients underwent cardiac surgery. One-year mortality was 8% (42% for HBAT; P < .001), 1.4% of patients relapsed, and 10.9% were readmitted during the first 3 months after discharge (no significant differences compared with HBAT). Charlson score (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.04-1.42; P = .01) and cardiac surgery (OR, 0.24; 95% CI, .09-.63; P = .04) were associated with 1-year mortality, whereas aortic valve involvement (OR, 0.47; 95% CI, .22-.98; P = .007) was the only predictor of 1-year readmission. Failing to fulfill IDSA criteria was not a risk factor for mortality or readmission. CONCLUSIONS: OPAT provided excellent results despite the use of broader criteria than those recommended by IDSA. OPAT criteria should therefore be expanded.

Antimicrobial management of Tropheryma whipplei endocarditis: the Spanish Collaboration on Endocarditis (GAMES) experience.

OBJECTIVES: Tropheryma whipplei has been detected in 3.5% of the blood culture-negative cases of endocarditis in Spain. Experience in the management of T. whipplei endocarditis is limited. Here we report the long-term outcome of the treatment of previously reported patients who were diagnosed with infective endocarditis (IE) caused by T. whipplei from the Spanish Collaboration on Endocarditis-Grupo de Apoyo al Manejo de la Endocarditis Infecciosa en España (GAMES) and discuss potential options for antimicrobial therapy for IE caused by T. whipplei. PATIENTS AND METHODS: Seventeen patients with T. whipplei endocarditis were recruited between 2008 and 2014 in 25 Spanish hospitals. Patients were classified according to the therapeutic regimen: ceftriaxone and trimethoprim/sulfamethoxazole, doxycycline + hydroxychloroquine and other treatment options. RESULTS: Follow-up data were obtained from 14 patients. The median follow-up was 46.5 months. All patients completed the antibiotic treatment prescribed, with a median duration of 13 months. Six patients were treated with ceftriaxone and trimethoprim/sulfamethoxazole (median duration 13 months), four with doxycycline + hydroxychloroquine (median duration 13.8 months) and four with other treatment options (median duration 22.3 months). The follow-up after the end of the treatments was between 5 and 84 months (median 24 months). CONCLUSIONS: All treatment lines were effective and well tolerated. Therapeutic failures were not detected during the treatment. None of the patients died or experienced a relapse during the follow-up. Only six patients received antibiotic treatment in accordance with guidelines. These data suggest that shorter antimicrobial treatments could be effective.

Epidemiological and clinical characteristics of Streptococcus tigurinus endocarditis.

BACKGROUND: Streptococcus tigurinus was recently described as a new streptococcal species within the viridans group streptococci (VGS). The objectives of the present work were to analyse the clinical and microbiological characteristics of S. tigurinus isolated from patients with bacteraemias, to determine the prevalence of S. tigurinus among VGS endocarditis in Spain, and to compare the clinical characteristics and outcomes of endocarditis caused by S. tigurinus and other VGS. METHODS: Retrospective nationwide study, performed between 2008 and 2016 in 9 Spanish hospitals from 7 different provinces comprising 237 cases of infective endocarditis. Streptococcal isolates were identified by sequencing fragments of their 16S rRNA, sodA and groEL genes. Clinical data of patients with streptococcal endocarditis were prospectively collected according to a pre-established protocol. RESULTS: Patients with endocarditis represented 7/9 (77.8%) and 26/86 (30.2%) of the bacteraemias caused by S. tigurinus and other VGS, respectively (p < 0.001), in two of the hospital participants. Among patients with streptococcal endocarditis, 12 different Streptococcus species were recognized being S. oralis, S. tigurinus and S. mitis the three more common. No relevant statistical differences were observed in the clinical characteristics and outcomes of endocarditis caused by the different VGS species. CONCLUSIONS: In this multicenter study performed in Spain, S. tigurinus showed a higher predilection for the endocardial endothelium as compared to other VGS. However, clinical characteristics and outcomes of endocarditis caused by S. tigurinus did not significantly differ from endocarditis caused by other oral streptococci.

Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Carbapenem-Resistant Organisms.

Ceftazidime-avibactam (CAZ-AVI) is a recently approved ß-lactam-ß-lactamase inhibitor combination with the potential to treat serious infections caused by carbapenem-resistant organisms. Few patients with such infections were included in the CAZ-AVI clinical trials, and clinical experience is lacking. We present a case series of patients with infections caused by carbapenem-resistant Enterobacteriaceae (CRE) or Pseudomonas aeruginosa (CRPa) who were treated with CAZ-AVI salvage therapy on a compassionate-use basis. Physicians who had prescribed CAZ-AVI completed a case report form. We used descriptive statistics to summarize patient characteristics and treatment outcomes. We used the Wilcoxon rank sum test and Fisher's exact test to compare patients by treatment outcome. The sample included 36 patients infected with CRE and two with CRPa. The most common infections were intra-abdominal. Physicians categorized 60.5% of patients as having life-threatening infections. All but two patients received other antibiotics before CAZ-AVI, for a median of 13 days. The median duration of CAZ-AVI treatment was 16 days. Twenty-five patients (65.8%) concurrently received other antibiotics to which their pathogen was nonresistant in vitro Twenty-eight patients (73.7%, 95% confidence interval [CI], 56.9 to 86.6%) experienced clinical and/or microbiological cure. Five patients (20.8%) with documented microbiological cure died, whereas 10 patients (71.4%) with no documented microbiological cure died (P = 0.01). In three-quarters of cases, CAZ-AVI (alone or combined with other antibiotics) cured infections caused by carbapenem-resistant organisms, 95% of which had failed previous therapy. Microbiological cure was associated with improved survival. CAZ-AVI shows promising clinical results for infections for which treatment options are limited.

Neutropenia during therapy with peginterferon and ribavirin in HIV-infected subjects with chronic hepatitis C and the risk of infections.

BACKGROUND: It is unclear whether pegylated interferon (peg-IFN) -induced neutropenia in subjects coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is associated with increased risk of serious infections. METHODS: This was a prospective cohort study conducted between 2000 and 2012 in HIV/HCV-coinfected subjects initiating treatment with peg-IFN plus ribavirin (RBV). Infections were defined as serious when patients required hospitalization, treatment was discontinued, or the patient died. The association between neutropenia (severe, <500 cells/µL; nonsevere, 500 -1500 cells/µL) and infections (serious infections and infections of any severity) was determined by logistic regression analysis. RESULTS: Among 418 subjects (3928 person-weeks of therapy), infections occurred in 123 (29%), accounting for 149 episodes (3.8 infections per 100 person-weeks of therapy). Most infections (47%) involved the upper respiratory tract and were minor. After a multivariate analysis adjusted by age, sex, CD4 count, AIDS, antiretroviral therapy, cirrhosis, neutrophil count, type of peg-IFN, and granulocyte colony-stimulating factor use, none of these variables remained independently associated with the risk of infection. Twenty subjects developed a serious infection (4.8% of all patients). The frequency of serious infections was higher in subjects with severe neutropenia compared to those with nonsevere neutropenia and without neutropenia, although it was not statistically significant (8.6%, 4.8%, and 3.6%, respectively; trend test P = .281). In multivariate analysis, neutropenia was not independently associated with increased risk of serious infections. CONCLUSIONS: In this large prospective cohort of HIV/HCV-coinfected patients treated with peg-IFN plus RBV, serious infections were uncommon, nonfatal, and unrelated to peg-IFN -induced severe neutropenia.

Reidentification of Streptococcus bovis isolates causing bacteremia according to the new taxonomy criteria: still an issue?

All Streptococcus bovis blood culture isolates recovered from January 2003 to January 2010 (n = 52) at the Hospital Universitario Ramón y Cajal were reidentified on the basis of their genetic traits using new taxonomic criteria. Initial identification was performed by the semiautomatic Wider system (Fco. Soria-Melguizo, Spain) and the API 20 Strep system (bioMérieux, France). All isolates were reidentified by PCR amplification and sequencing of both the 16S rRNA and sodA genes and by mass spectrometry using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS; Bruker, Germany). Results of 16S rRNA/sodA gene sequencing were as follows: Streptococcus gallolyticus subsp. gallolyticus, 14/14 (number of isolates identified by 16S rRNA/number of isolates identified by sodA gene sequencing); Streptococcus gallolyticus subsp. pasteurianus, 24/24; Streptococcus spp., 7/0; Streptococcus infantarius subsp. infantarius, 0/2; Streptococcus lutetiensis, 0/5; Leuconostoc mesenteroides, 4/0; and Lactococcus lactis, 3/3. MALDI-TOF MS identified 27 S. gallolyticus isolates but not at the subspecies level, 4 L. mesenteroides isolates, 3 L. lactis isolates, and 6 S. lutetiensis isolates, whereas 12 isolates rendered a nonreliable identification result. Pulsed-field gel electrophoresis grouped all S. gallolyticus subsp. gallolyticus isolates into 3 major clusters clearly different from those of the S. gallolyticus subsp. pasteurianus isolates, which, in turn, exhibited no clonal relationship. The percentages of resistance to the tested antimicrobials were 38% for erythromycin, 23% for fosfomycin, 10% for levofloxacin, 6% for tetracycline, and 4% for co-trimoxazole. The most frequent underlying diseases were hepatobiliary disorders (53%), endocarditis (17%), and malignancies (12%). We conclude that sequencing of the sodA gene was the most discriminatory method and that S. gallolyticus subsp. pasteurianus appears to have a higher genetic diversity than S. gallolyticus subsp. gallolyticus.

Changes in the epidemiology of tuberculosis: the influence of international migration flows.

INTRODUCTION: The epidemiological characteristics of patients with tuberculosis (TB) in European hospitals have changed in recent years. METHODS: A prospective study of patients with culture-proven pulmonary TB admitted to our institution from 1997 to 2008 is shown. RESULTS: We analyzed 661 patients with pulmonary TB. An increase in the incidence of TB was confirmed during the study period (P<.001). The proportion of patients with HIV infection decreased from 26% during 1997-2000 to 12% during 2005-2008. However, the proportions of older (>40 years old) and foreign-born patients increased significantly, from 37% to 59% and from 12% to 35%, respectively. Multivariate analysis confirmed previous antituberculous therapy and immigration as factors associated with resistance to isoniazid and to isoniazid+rifampin. After the year 2000, mortality was independently associated with extrapulmonary TB (OR: 3.1; CI 95%: 1.4-7.2), hepatitis C virus infection (OR: 6.0; CI 95%: 2.2-16.3), and diabetes (OR: 6.4; CI 95%: 2.4-16.8). CONCLUSION: Immigration from countries with high rates of TB infection has replaced HIV infection as the most relevant risk factor associated with TB. The increase in the number of older patients with TB and the presence of specific comorbid conditions, especially chronic liver dysfunction, could explain the more difficult management and increased mortality.

Prevention, Diagnosis and Management of Post-Surgical Mediastinitis in Adults Consensus Guidelines of the Spanish Society of Cardiovascular Infections (SEICAV), the Spanish Society of Thoracic and Cardiovascular Surgery (SECTCV) and the Biomedical Research Centre Network for Respiratory Diseases (CIBERES).

This is a consensus document of the Spanish Society of Cardiovascular Infections (SEICAV), the Spanish Society of Thoracic and Cardiovascular Surgery (SECTCV) and the Biomedical Research Centre Network for Respiratory Diseases (CIBERES). These three entities have brought together a multidisciplinary group of experts that includes anaesthesiologists, cardiac and cardiothoracic surgeons, clinical microbiologists, infectious diseases and intensive care specialists, internal medicine doctors and radiologists. Despite the clinical and economic consequences of sternal wound infections, to date, there are no specific guidelines for the prevention, diagnosis and management of mediastinitis based on a multidisciplinary consensus. The purpose of the present document is to provide evidence-based guidance on the most effective diagnosis and management of patients who have experienced or are at risk of developing a post-surgical mediastinitis infection in order to optimise patient outcomes and the process of care. The intended users of the document are health care providers who help patients make decisions regarding their treatment, aiming to optimise the benefits and minimise any harm as well as the workload.

Observational study to evaluate clinical outcomes after first-line efavirenz-or lopinavir-ritonavir-based HAART in treatment-naive patients.

PURPOSE: To evaluate clinical, immunological, and virological outcomes after first-line highly active antiretroviral therapy (HAART) with a regimen including either efavirenz (EFV) or lopinavir/ritonavir (LPV/r) in treatment-naive adult patients in routine clinical care. METHOD: An ongoing prospective, observational follow-up study included all patients starting their first antiretroviral therapy (ART) with any of the studied regimens from July 1998 to July 2004. The follow-up period was finalized in September 2006, when all patients completed an observation of at least 96 weeks. Mortality rates, CD4 counts, viral suppression (HIV RNA below 50 copies/mL), and discontinuation of any component of the regimen were compared at 48 and 96 weeks. RESULTS: Despite the worst immunological status of the LPV/r group patients at baseline, this regimen was at least as effective as the one based on EFV not only in terms of treatment durability but also in terms of virological responses, nevertheless with an apparently quicker immune recovery. In general terms, both regimens present similar tolerability and safety outcomes except for the higher risk of increasing triglyceride (TG) levels in the LPV/r group. Low durability was observed in both regimens. CONCLUSION: In a routine clinical care setting, initial HAART containing LPV/r seems to present an effectiveness, tolerability, and toxicity similar to the one containing EFV.

Hypermucoviscous Klebsiella pneumoniae: A challenge in community acquired infection.

In 1986, a new syndrome was described in Taiwan secondary to hypervirulent K. pneumoniae (hvKP), and its main feature was the ability to cause severe infection in young and immunocompetent hosts. Their virulence is explained by the efficient acquisition of iron and an increase in capsule production, which confer the characteristic hypermucoviscous phenotype. Most of these cases have been described in Asia and subsequently spread to America and Europe, where their prevalence is much lower. We present four cases of bacteremia and liver abscesses secondary to hypervirulent K. pneumoniae, two of them associated with endophthalmitis. K. pneumoniae isolates recovered from two of the patients belonged to capsular serotype K1 (genes wzx_K1 and magA), while the other two were K2 (gene wzy_K2). Both of the K1 isolates were classified into a ST23, and isolates of serotype K2 belonged to the ST375 and ST881 clones. In Europe, hvKP isolates are less frequently recovered, mostly associated with Asian citizens or travelers, which was not the case in our patients. K1 capsular serotype is a major cause of primary liver abscess and secondary septic embolus, and K2 is associated with secondary liver abscess. Although these hypervirulent variants usually affect immunocompetent patients as in our cases, diabetes mellitus is a major risk factor for the most invasive cases, with concomitant poor prognosis. Identification of hypervirulent K. pneumoniae serotypes K1 and K2 should be considered as part of the microbiological diagnosis of community-acquired liver abscess due to their clinical implications.

Impact of a structured HIV testing program in a hospital emergency department and a primary care center.

INTRODUCTION: HIV testing guidelines are poorly implemented in most clinical settings. The best screening strategy and healthcare scenario are still unknown. The aim of our study is to evaluate the impact of a structured HIV testing intervention (DRIVE), compared to HIV testing as routinely performed in clinical practice, in two different clinical settings: a primary care center and an emergency department. METHODS: Prospective evaluation of an HIV testing strategy in two clinical settings from the same healthcare area. The DRIVE program included trained nurse practitioners to perform the screening, a questionnaire to assess the risk of exposure and HIV indicator conditions (RE&IC), and rapid HIV tests. The main variables between the DRIVE program and clinical practice were the absolute number of newly diagnosed HIV infections and testing coverage. RESULTS: The DRIVE program included 5,329 participants, of which 51.2% reported at least one positive answer in the questionnaire. The estimated HIV testing coverage was significantly higher in the DRIVE program than in the routine clinical practice (7.17% vs. 0.96%, p < 0.001), and was better in the primary care center than in the emergency department with the two strategies. Twenty-two HIV-positive people were identified, with a rate of 8.6‰ in the emergency department vs. 2.2‰ in the primary care center (p = 0.001). A higher rate of new HIV diagnoses was found in the DRIVE program compared to routine clinical practice (29.6 vs. 3.1 per 100,000 patients attended; p < 0.001). CONCLUSIONS: An easy-to-implement, structured intervention increased the absolute number of new HIV diagnoses and HIV tests, compared to routine clinical practice.

Brief communication: treatment of Enterococcus faecalis endocarditis with ampicillin plus ceftriaxone.

BACKGROUND: High-level aminoglycoside resistance (HLAR) that precludes bactericidal synergism with penicillins or glycopeptides and nephrotoxicity related to aminoglycoside treatment are major problems in treating Enterococcus faecalis endocarditis. OBJECTIVE: To evaluate the efficacy and safety of ampicillin plus ceftriaxone for treating endocarditis due to E. faecalis with and without HLAR. DESIGN: Observational, open-label, nonrandomized, multicenter clinical trial. SETTING: 13 centers in Spain. PATIENTS: 21 patients with HLAR E. faecalis endocarditis and 22 patients with non-HLAR E. faecalis endocarditis. All were at risk for nephrotoxicity related to aminoglycoside use. INTERVENTION: 6-week course of intravenous ampicillin, 2 g every 4 hours, plus intravenous ceftriaxone, 2 g every 12 hours. MEASUREMENTS: Clinical and microbiological outcomes. RESULTS: The clinical cure rate at 3 months was 67.4% (29 of 43 patients) among all episodes. During treatment, 28.6% of patients with HLAR E. faecalis endocarditis and 18.2% of patients with non-HLAR E. faecalis endocarditis died of infection-related causes. The rate of clinical and microbiological cure in patients who completed the protocol was 100% in the HLAR E. faecalis endocarditis group. No episodes of breakthrough bacteremia occurred, although there were 2 relapses in the non-HLAR E. faecalis endocarditis group. Treatment was withdrawn in 1 case because of fever and skin rash. LIMITATIONS: The study had a small sample and was observational. CONCLUSION: The combination of ampicillin and ceftriaxone is effective and safe for treating HLAR E. faecalis endocarditis and could be a reasonable alternative for patients with non-HLAR E. faecalis endocarditis who are at increased risk for nephrotoxicity.

Treatment of infections caused by nontuberculous mycobacteria. / Tratamiento de las infecciones producidas por micobacterias no tuberculosas.

Nontuberculous mycobacteria are a heterogeneous group of microorganisms that can often cause human infection, although they may also be considered to be contaminants or colonisers on occasions. The management of these infections must necessarily take into account the identification of isolated species and their in vitro susceptibility testing (although not for all of them), as well as the characteristics of the patient, because these treatments are usually prolonged and must be carried out by experts in the management of these infections. Classically divided into slowly growing mycobacteria and rapidly growing mycobacteria, the treatment regimens and the antibiotics used are different for both groups. In addition, in certain circumstances, this treatment must necessarily be linked to other measures (removal of foreign bodies, surgery) in order to maximise the likelihood of curing the patient.

Mortality risk prediction in infective endocarditis surgery: reliability analysis of specific scores.

OBJECTIVES: We assessed the prognostic utility of risk scores in surgery for infective endocarditis (IE) to evaluate their reliability in mortality risk prediction. METHODS: An observational retrospective study was developed to include all patients who underwent surgery for active IE from 2002 to 2016. Classical and endocarditis-specific risk scores were calculated. RESULTS: A total of 180 patients were included in the study. The 30-day mortality rate was 26.82% [95% confidence interval (CI) 20.26-33.20%]. Classical risk scores were confirmed to have a suboptimal prognostic ability. Therefore, 4 IE-specific risk scores were calculated. Discrimination was evaluated using the area under the receiver operating characteristic curve. It was 0.76 (95% CI 0.68-0.82) for the Society of Thoracic Surgeons-IE (STS-IE) score; 0.68 (95% CI 0.58-0.76) for the De Feo-Cotrufo score; 0.73 (95% CI 0.66-0.79) for the PALSUSE score and 0.65 (95% CI 0.57-0.72) for the Costa score. The STS-IE score had higher discrimination when compared with the De Feo-Cotrufo score (P = 0.055) and the Costa score (P = 0.024); however, there was no significant difference when we compared the STS-IE score with the PALSUSE score (P = 0.58). Calibration was assessed using the Hosmer-Lemeshow test; an adequate calibration was confirmed in all 4 scores. CONCLUSIONS: Specific risk scores had better prognostic performance than classical risk scores. The STS-IE score had the highest discrimination and was adequately calibrated. The PALSUSE score also showed optimal discrimination and calibration. The De Feo-Cotrufo score had a lower discrimination in our sample; however, the De Feo-Cotrufo score is recommended in the current guidelines. The Costa score had the lowest discrimination.

Infective Endocarditis in Patients With Bicuspid Aortic Valve or Mitral Valve Prolapse.

BACKGROUND: There is little information concerning infective endocarditis (IE) in patients with bicuspid aortic valve (BAV) or mitral valve prolapse (MVP). Currently, IE antibiotic prophylaxis (IEAP) is not recommended for these conditions. OBJECTIVES: This study sought to describe the clinical and microbiological features of IE in patients with BAV and MVP and compare them with those of IE patients with and without IEAP indication, to determine the potential benefit of IEAP in these conditions. METHODS: This analysis involved 3,208 consecutive IE patients prospectively included in the GAMES (Grupo de Apoyo al Manejo de la Endocarditis infecciosa en España) registry at 31 Spanish hospitals. Patients were classified as high-risk IE with IEAP indication (high-risk group; n = 1,226), low- and moderate-risk IE without IEAP indication (low/moderate-risk group; n = 1,839), and IE with BAV (n = 54) or MVP (n = 89). RESULTS: BAV and MVP patients had a higher incidence of viridans group streptococci IE than did high-risk group and low/moderate-risk group patients (35.2% and 39.3% vs. 12.1% and 15.0%, respectively; all p < 0.01). A similar pattern was seen for IE from suspected odontologic origin (14.8% and 18.0% vs. 5.8% and 6.0%; all p < 0.01). BAV and MVP patients had more intracardiac complications than did low/moderate-risk group (50% and 47.2% vs. 30.6%, both p < 0.01) patients and were similar to high-risk group patients. CONCLUSIONS: IE in patients with BAV and MVP have higher rates of viridans group streptococci IE and IE from suspected odontologic origin than in other IE patients, with a clinical profile similar to that of high-risk IE patients. Our findings suggest that BAV and MVP should be classified as high-risk IE conditions and the case for IEAP should be reconsidered.

Trends in neurological complications of endocarditis.

Neurological complications (NCs) are a major cause of morbidity and mortality in patients with infectious endocarditis (IE). The frequency of these complications has been found to remain constant since the preantibiotic era despite profound epidemiological changes and therapeutic advances. We have reviewed retrospectively all the cases of IE attended at a single institution between 1985 and 2003, aiming to study the clinical characteristics of the NCs, and to analyse possible temporal trends in their frequency. Among 550 patients with IE, 71 (13%) suffered NCs. NCs presented more frequently in native (NVE) and prosthetic (PVE) valve endocarditis (17% and 20%, respectively) than in endocarditis associated with drug addiction (IDU-NVE) or pacemeker (6% and 9%, respectively). Cerebrovascular disorders were the most frequent NCs (60% of the patients had ischemic events and 21% had haemorrhages). Meningitis and cerebral abscess occurred in 16% and 3% of patients with NCs, respectively, and diffuse encephalopathy in 13%. Staphylococus aureus infection was the only factor associated with NCs, but only in NVE. During the study period there was a trend for increasing frequency of NCs in IE patients, probably associated to several factors: a decrease in IDUNVE, an increase in more aggressive nosocomial acquired NVE, and an increase in NVE caused by S. aureus. Mortality among patients with NCs (34%) was significantly higher than in IE patients without them (11%). During the study period mortality increased in patients with NVE and NCs.

Latent tuberculosis infection: approach and therapeutic schemes

Tuberculosis continues to be a major public health problem. A priority objective is the implementation of early diagnosis, contact investigation and latent tuberculosis infection (LTBI) testing. World Health Organization (WHO) concludes that there is no gold standard for the diagnosis of LTBI; both the tuberculin test and IGRA (interferon gamma release assays) indirectly identify tuberculosis infection; both tests are considered acceptable but imperfect. WHO recommends that regimens that include rifamycins are equally effective but less toxic and more adherent than long regimens with isoniazid. (AU)