Lung Transplantation in Pulmonary Hypertension: A Multidisciplinary Unit's Management Experience.

BACKGROUND: Prognosis assessment of pulmonary hypertension (PH) is multifactorial and placement of patients on the lung transplantation (LT) waiting list requires the weighing of a complex set of criteria. The aim of this retrospective cohort study was to analyze a series of patients treated in our unit at the moment of their inclusion on the LT waiting list and long-term survival after LT. MATERIAL AND METHODS: Baseline characteristics, LT outcomes, and survival were evaluated in all patients diagnosed with pulmonary arterial hypertension (PAH) and pulmonary veno-occlusive disease (PVOD) who were included on the LT waiting list in 2011-2016. RESULTS: Thirty-three patients were listed with a diagnosis of PAH or PVOD. Patients had an average age of 43 ± 12 years and 71% were female. The median time between PAH diagnosis and inclusion on the LT waiting list was 62.5 months (interquartile range [IQR], 6-93.3 months). Twenty-eight patients (84%) underwent double LT. The difference between the waiting time in urgent cases (1.5 months; IQR, 0.4-4.2 months) and in elective cases (7.4 months; IQR, 2.7-16.2 months) was significant (P < .049). The 28 patients with PAH/PVOD in our hospital had a 95% short-term survival after LT both at 1 and at 3 months, without variance between urgent and elective LT. Longer-term survival rate was 84% both at 12 and 36 months. CONCLUSIONS: There is great complexity in determining the appropriate time for transplantation referral and inclusion on the waiting list for patients with PAH/PVOD so that LT can be more realistically incorporated into the treatment algorithm for PAH. LT offers a good short- and long-term survival in patients with PAH/PVOD.

Impact of the Xpert(®) MTB/RIF molecular test on the late diagnosis of pulmonary tuberculosis.

We analysed the impact of the Xpert(®) MTB/RIF molecular test on health-care diagnostic delay among tuberculosis patients. Diagnostic delay was 17.2 days (standard deviation 23.2, median 10 days). Of 128 patients recruited into the study, 60 (47%) were smear-negative; of these, 40 (67%) were Xpert-positive and were started on treatment without culture. The sensitivity of smear microscopy was 53% compared with 82% for Xpert. In smear-negative patients, delay in Xpert-positive and -negative patients was respectively 15.5 ± 13.2 and 25.5 ± 12.5 days (P = 0.002). We conclude that Xpert results were significantly associated with shorter health-care diagnostic delay, particularly in smear-negative patients.

Safety and immunogenicity of one dose of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, when administered to adolescents concomitantly or sequentially with Tdap and HPV vaccines.

This Phase III study evaluates an investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM (Novartis Vaccines), when administered concomitantly or sequentially with two other recommended adolescent vaccines; combined tetanus, reduced diphtheria and acellular pertussis (Tdap), and human papillomavirus (HPV) vaccine. In this single-centre study, 1620 subjects 11-18 years of age, were randomized to three groups (1:1:1) to receive MenACWY-CRM concomitantly or sequentially with Tdap and HPV. Meningococcal serogroup-specific serum bactericidal assay using human complement (hSBA), and antibodies to Tdap antigens and HPV virus-like particles were determined before and 1 month after study vaccinations. Proportions of subjects with hSBA titres > or =1:8 for all four meningococcal serogroups (A, C, W-135, Y) were non-inferior for both concomitant and sequential administration. Immune responses to Tdap and HPV antigens were comparable when these vaccines were given alone or concomitantly with MenACWY-CRM. All vaccines were well tolerated; concomitant or sequential administration did not increase reactogenicity. MenACWY-CRM was well tolerated and immunogenic in subjects 11-18 years of age, with comparable immune responses to the four serogroups when given alone or concomitantly with Tdap or HPV antigens. This is the first demonstration that these currently recommended adolescent vaccines could be administered concomitantly without causing increased reactogenicity.

Microbiology of acute otitis media in Costa Rican children.

BACKGROUND: Because of the increasing number of resistant middle ear pathogens reported from different centers worldwide, an active surveillance of the microbiology and susceptibility pattern of middle ear pathogens is required for proper antimicrobial recommendations among different regions of the world. OBJECTIVE: To study the microbiology and susceptibility pattern of middle ear pathogens obtained from Costa Rican children with acute otitis media. METHODS: Between 1992 and 1997 a diagnostic tympanocentesis was performed in 398 Costa Rican patients with acute otitis media. Middle ear fluid was obtained for culture and minimal inhibitory concentrations were determined by the E-test technique in those isolates obtained between October, 1995, and January, 1997. RESULTS: The most common pathogens cultured were Streptococcus pneumoniae (30%), Haemophilus influenzae (14%), Staphylococcus aureus (4%) and Streptococcus pyogenes (4%). Moraxella catarrhalis was uncommon. Beta-lactamase production was low (3.7%) among the H. influenzae isolates but frequent among the Staphylococcus aureus (57.1%) and M. catarrhalis (100%) strains. Overall 9 of 46 S. pneumoniae isolates (19.6%) exhibited decreased susceptibility to penicillin of which 8 isolates (17.4%) showed intermediate and one strain (2.2%) high level resistance. Among the penicillin-susceptible S. pneumoniae isolates, susceptibility to the following antimicrobials was: 81%, azithromycin; 89%, clarithromycin; and 100%, ceftriaxone and trimethoprim-sulfamethoxazole (TMP-SMX). Among the penicillin-resistant S. pneumoniae isolates the percentage of susceptible strains was 89% for azithromycin, clarithromycin and ceftriaxone and 67% for TMP-SMX. CONCLUSIONS: Based on this microbiologic information the agents considered first line drugs in the treatment of acute otitis media in Costa Rica remain amoxicillin or TMP-SMX.

Comparative trial of 3 days of azithromycin versus 10 days of clarithromycin in the treatment of children with acute otitis media with effusion.

The authors compared the efficacy, safety and tolerance of azithromycin and clarithromycin in pediatric patients with acute otitis media. A randomized, open clinical trial was performed comparing azithromycin and clarithromycin in children aged 6 months to 12 years of age with acute otitis media with effusion. Patients were allocated to azithromycin at 10 mg/kg once daily for 3 days or to clarithromycin at 15 mg/kg day divided into two equal doses for 10 days. Clinical examinations and tympanometric evaluations were performed at baseline, day 3-5, day 10-14, day 28-30 and day 50-60. Tympanocentesis fluid cultures were collected at enrollment and urine and blood samples were obtained at baseline and day 10-14. Of 100 patients enrolled, 97 were considered evaluable. The most common middle ear pathogens were Streptococcus pneumoniae (60%), Haemophilus influenzae (15%) and Staphylococcus aureus (13%). Fifty patients (100%) treated with azithromycin and 45 (95.7%) patients treated with clarithromycin had a satisfactory clinical response. Rates of persistence of middle ear effusion and possible drug related side effects were comparable. Based on the efficacy and safety results, azithromycin for 3 days and clarithromycin for 10 days are considered to represent an attractive alternative for the treatment of children with acute otitis media.

Comparative trial of 3-day azithromycin versus 10-day amoxycillin/clavulanate potassium in the treatment of children with acute otitis media with effusion.

A randomized, open clinical trial was performed to compare azithromycin and amoxycillin/clavulanate potassium in children with acute otitis media with effusion. Patients were allocated to therapy with azithromycin (10 mg/kg once daily for 3 days) or amoxycillin/clavulanate potassium (40 mg/kg/day divided into three equal doses for 10 days). Clinical examination and tympanometric evaluation were performed at baseline, and at day 3 to 5, day 10 to 14, day 28 to 30 and day 55 to 60 after the initiation of therapy. Tympanocentesis fluid cultures were collected at enrolment, and urine and blood samples were obtained at baseline and at day 10 to 11. Of 100 patients enrolled, 92 were considered evaluable. Middle ear cultures were positive in 53.2% of the patients; the most common pathogens were Streptococcus pneumoniae (33%) and Haemophilus influenzae (33%). The response was satisfactory in 47 (100%) patients treated with azithromycin and 42 (95.4%) patients receiving A/C. Rates of persistence of middle ear effusion were comparable. Nausea and loose stools were more common in children treated with amoxycillin/clavulanate potassium (P < or = 0.02). Based on the comparable efficacy noted in this study, the lower incidence of side-effects and the convenience of a shorter duration of treatment, azithromycin represents an attractive therapeutic alternative to amoxycillin/clavulanate potassium and should be further evaluated in larger-scale clinical trials including patients with penicillin-resistant organisms.

An open, multicenter clinical trial of piperacillin/tazobactam in the treatment of pediatric patients with intra-abdominal infections.

A total of 60 children with secondary peritonitis were enrolled in an open, non-comparative multicenter study designed to evaluate the safety, tolerance and efficacy of parenteral piperacillin/tazobactam (80/10 mg/kg every 8 hours) in young children. The most common diagnosis was perforated appendicitis (90%) and the three most common pathogens, obtained from the peritoneal cavity, were Escherichia coli (52 isolates), Pseudomonas aeruginosa (16 isolates) and Bacteroides sp. (19 isolates). Patients were examined daily during therapy, 4-14 days and 4-6 weeks post-therapy. Of the 60 patients, 43 were evaluable. The majority of patients had polymicrobial infections (36 patients). All the aerobic isolates were susceptible to piperacillin/tazobactam while 19 were resistant to piperacillin alone. Four of 43 clinically evaluable patients were considered a clinical failure and 3 of 40 bacteriologically evaluable patients were considered to have an unfavorable microbiological response. There were 2 clinically adverse events considered related to the study drug and several possibly related, mild and transitory, abnormalities in eosinophil counts and liver function tests. Based on the safety and efficacy results from this study, the advantages of using a single agent for the treatment of mixed infections of the peritoneal cavity and its potential activity against resistant organisms, we believe that further comparative clinical trials in children with intra-abdominal infections are warranted.

Antimicrobial therapy for children with chronic suppurative otitis media without cholesteatoma.

This study was designed to determine the middle ear bacterial pathogens, the frequency of serum immunoglobulin deficiency and the efficacy of medical management in patients with chronic suppurative otitis media without cholesteatoma. This was an open noncomparative clinical trial performed at the National Children's Hospital, San Jose, Costa Rica, and included 186 patients older than 2 months of age with a confirmed diagnosis of chronic suppurative otitis media without cholesteatoma. Middle ear cultures and serum for immunoglobulin determinations were obtained on admission. The first 40 patients were treated only with ceftazidime and from patient 41 and up, if a Gram-positive organism was cultured, oxacillin was added to (for combined infection) or replaced ceftazidime. Parenteral antibiotics and suction twice daily were continued until three days after the middle ear became dry. Trimethropimsulfamethoxazole prophylaxis was administered during the follow-up period. Middle ear bacterial cultures were positive in 166 patients. Pseudomonas sp. (35.6%), enteric Gram-negative organisms (28.7%) and Gram-positive cocci (26%) were the most common organisms. Immunoglobulin determinations were below normal in 3 of 69 (4.3%) evaluable patients. Dryness of the ear was achieved in 174 patients (93.5%) including 130 of 139 patients treated with ceftazidime, 28 of 28 patients treated with oxacillin and 14 of 14 patients treated with ceftazidime and oxacillin. Recurrent otorrhea developed in 39 (23.4%) patients. Twice-daily canal aspiration and parenteral ceftazidime for Gram-negative organisms and/or oxacillin for Gram-positive bacteria for 3 days after dryness of the middle ear followed by prophylactic oral antimicrobials are effective for treatment of most chronic suppurative otitis media without cholesteatoma patients.