Identification of Streptococcus pneumoniae in hospital-acquired pneumonia in adults.

Hospital-acquired pneumonia (HAP) is often more severe and life-threatening than community-acquired pneumonia (CAP). The role of Streptococcus pneumoniae in CAP is well-understood, but its role in HAP is unclear. The objective of this study was to summarize the available literature on the prevalence of S. pneumoniae in HAP episodes. We searched MEDLINE for peer-reviewed articles on the microbiology of HAP in individuals aged ≥18 years, published between 2008 and 2018. We calculated pooled estimates of the prevalence of S. pneumoniae in episodes of HAP using a random-effects, inverse-variance-weighted meta-analysis. Forty-seven of 1908 articles met the inclusion criteria. Bacterial specimen isolation techniques for microbiologically defined HAP episodes included bronchoalveolar lavage, protective specimen brush, tracheobronchial aspirate and sputum, as well as blood culture. Culture was performed in all studies; five studies also used urine antigen detection (5/47; 10.6%). S. pneumoniae was identified in 5.1% (95% confidence interval (CI): 3.8-6.6%) of microbiologically defined HAP episodes (N = 20), with 5.4% (95% CI: 4.3-6.7%, N = 29) in ventilator-associated HAP and 6.0% (95% CI: 4.1-8.8%, N = 6) in non-ventilator-associated HAP. S. pneumoniae was identified in 5.3% (95% CI: 4.5-6.3%) of HAP occurring in the intensive care unit (ICU, N = 41) and in 5.6% (95% CI: 3.3-9.5%, N = 5) outside the ICU. A higher proportion of early-onset HAP (10.3%; 95% CI: 8.3-12.8%, N = 16) identified S. pneumoniae as compared with late-onset HAP (3.3%; 95% CI: 2.5-4.4%, N = 16). In conclusion, S. pneumoniae was identified by culture in 5.1% of microbiologically defined HAP episodes. The importance of HAP as part of the disease burden caused by S. pneumoniae merits further research.

Otitis media across nine countries: disease burden and management.

OBJECTIVE: To assess the perceived disease burden and management of otitis media (OM) among an international cohort of experienced physicians. METHODS: A cross-sectional survey conducted in France, Germany, Spain, Poland, Argentina, Mexico, South Korea, Thailand and Saudi Arabia. Face-to-face interviews conducted with 1800 physicians (95% paediatricians, 5% family practitioners).Main outcome measures were the perceived burden on clinical practice (number of cases, complications and referrals) and first- and second-line management strategies for OM. Results are expressed as mean and range across the nine countries over three continents. RESULTS: Respondents estimated an average annual caseload of 375 (range 128-1003) children under 5 years of age with OM; 54% (range 44-71%) with an initial episode and 38% (range 27-54%) with recurrent OM (ROM). OM with complications was estimated to be approximately 20 (range 7-49) cases per year and an estimated 15% (8-41%) of children with OM was recalled as needing specialist referral. There was high awareness of Streptococcus pneumoniae and Haemophilus influenzae as causative bacterial pathogens: 77% (range 65-91%) and 74% (range 68-83%), respectively, but less recognition of non-typeable H. influenzae (NTHi); 59% (range 45-67%). Although concern over antimicrobial resistance was widespread, empirical treatment with antibiotics was the most common first-line treatment (mean 81%, range 40-96%). The burden of disease is substantial enough that many physicians would consider vaccination to prevent OM (mean score 5.1, range 4.3-6.2 on 1-7 scale). CONCLUSIONS: This large, multinational survey shows that OM remains a significant burden for clinical practice. Despite awareness of shortcomings, antimicrobial therapy remains the most frequent treatment for OM.

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.

Pharmacokinetics and safety of famciclovir in children with herpes simplex or varicella-zoster virus infection.

Two multicenter, open-label, single-arm, two-phase studies evaluated single-dose pharmacokinetics and single- and multiple-dose safety of a pediatric oral famciclovir formulation (prodrug of penciclovir) in children aged 1 to 12 years with suspicion or evidence of herpes simplex virus (HSV) or varicella-zoster virus (VZV) infection. Pooled pharmacokinetic data were generated after single doses in 51 participants (approximately 12.5 mg/kg of body weight [BW] for children weighing < 40 kg and 500 mg for children weighing > or = 40 kg). The average systemic exposure to penciclovir was similar (6- to 12-year-olds) or slightly lower (1- to < 6-year-olds) than that in adults receiving a 500-mg dose of famciclovir (historical data). The apparent clearance of penciclovir increased with BW in a nonlinear manner, proportional to BW(0.696). An eight-step weight-based dosing regimen was developed to optimize exposure in smaller children and was used in the 7-day multiple-dose safety phases of both studies, which enrolled 100 patients with confirmed/suspected viral infections. Twenty-six of 47 (55.3%) HSV-infected patients who received famciclovir twice a day and 24 of 53 (45.3%) VZV-infected patients who received famciclovir three times a day experienced at least one adverse event. Most adverse events were gastrointestinal in nature. Exploratory analysis following 7-day famciclovir dosing regimen showed resolution of symptoms in most children with active HSV (19/21 [90.5%]) or VZV disease (49/53 [92.5%]). Famciclovir formulation (sprinkle capsules in OraSweet) was acceptable to participants/caregivers. In summary, we present a weight-adjusted dosing schedule for children that achieves systemic exposures similar to those for adults given the 500-mg dose.

Losartan attenuates bleomycin induced lung fibrosis by increasing prostaglandin E2 synthesis.

BACKGROUND: The angiotensin system has a role in the pathogenesis of pulmonary fibrosis. This study examines the antifibrotic effect of losartan, an angiotensin II type 1 receptor antagonist, in bleomycin induced lung fibrosis and its possible implication in the regulation of prostaglandin E(2) (PGE(2)) synthesis and cyclooxygenase-2 (COX-2) expression. METHODS: Rats were given a single intratracheal instillation of bleomycin (2.5 U/kg). Losartan (50 mg/kg/day) was administrated orally starting one day before induction of lung fibrosis and continuing to the conclusion of each experiment. RESULTS: Losartan reduced the inflammation induced by bleomycin, as indicated by lower myeloperoxidase activity and protein content in the bronchoalveolar lavage fluid. Collagen deposition induced by bleomycin was inhibited by losartan, as shown by a reduction in the hydroxyproline content and the amelioration of morphological changes. PGE(2) levels were lower in fibrotic lungs than in normal lungs. Losartan significantly increased PGE(2) levels at both 3 and 15 days. A reduction in COX-2 expression by bleomycin was seen at 3 days which was relieved by losartan. CONCLUSIONS: The antifibrotic effect of losartan appears to be mediated by its ability to stimulate the production of PGE(2). Losartan, which is already widely used clinically, could be assessed as a new treatment in lung fibrosis.

Evaluación del grado de satisfacción de las pacientes atendidas por el área de cirugía en la UCSI de un hospital maternal / Evaluation of the degree of satisfaction of patients treated in the ambulatory surgical unit of a maternity hospital

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Evolución del índice de sustitución por procesos en la UCSI de un hospital maternal universitario desde enero del 2000 a junio del 2003 / Evolution of the substitution index by procedures in the ambulatory surgical unit of a university maternity hospital between january 2000 and june 2003

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[Dendriform pulmonary ossification associated with idiopathic pulmonary fibrosis]. / Osificación pulmonar dendriforme asociada con fibrosis pulmonar idiopática.

Diffuse pulmonary ossification, a rare condition characterized by metaplastic ossification of the lung, is usually associated with diseases causing diffuse pulmonary lesions. Two types dendriform and nodular have been identified. In dendriform ossification, the less common type, osseous ramifications occur along the distal airways, with occasional islets of bone marrow. We report a case of diffuse dendriform pulmonary ossification associated with idiopathic pulmonary fibrosis. The diagnosis was based on histological examination, which demonstrated multiple nodules and ramified osseous spicules around the lung, mainly at the lower lobes, where the fibrotic lesions were also most evident.

Osificación pulmonar dendriforme asociada con fibrosis pulmonar idiopática / Dendriform pulmonary ossification associated with idiopathic pulmonary fibrosis

La osificación pulmonar difusa es una entidad poco frecuente en la que se produce una metaplasia ósea del pulmón y que suele asociarse con enfermedades que ocasionan lesiones pulmonares difusas. Existen dos tipos de osificación pulmonar: la dendriforme y la nodular. La forma dendriforme es la menos frecuente y se caracteriza por ramificaciones de estructura ósea a lo largo de las vías aéreas distales con islotes ocasionales de médula ósea. Se presenta un caso de osificación pulmonar difusa de tipo dendriforme asociada con fibrosis pulmonar idiopática. El diagnóstico se estableció mediante el examen histológico, que demostró la presencia de múltiples nódulos y espículas óseas ramificadas en la periferia del pulmón, principalmente en los lóbulos pulmonares inferiores, donde las lesiones fibróticas eran más evidentes. (AU)

Bacteriologic and clinical efficacy of high dose amoxicillin/clavulanate in children with acute otitis media.

OBJECTIVES: To determine the bacteriologic and clinical efficacy of high dose amoxicillin/clavulanate (90/6.4 mg/kg/day) against common bacterial pathogens causing acute otitis media (AOM), including penicillin-resistant Streptococcus pneumoniae (PRSP). METHODS: In this open label multicenter study, 521 infants and children with AOM [mean age, 18.6 months; age < 24 months, n = 375 (72%)] were treated with amoxicillin/clavulanate 90/6.4 mg/kg/day in two divided doses for 10 days. Bilateral otitis media, previous episodes of AOM, antibiotic treatment within 3 months and day-care attendance were recorded in 60.1, 35.7, 50.2 and 38.2% of the children, respectively. Tympanocentesis was performed before the first dose and repeated on Days 4 to 6 for all children with S. pneumoniae at 22 centers and for all children with any pathogen at 3 centers. Clinical response was assessed at end of therapy. RESULTS: Pathogens were isolated from 355 (68%) of 521 enrolled children; 180 children underwent repeat tympanocentesis and were bacteriologically evaluable. Baseline pathogens were S. pneumoniae (n = 122 enrolled/93 bacteriologically evaluable), Haemophilus influenzae (n = 160/51), both (n = 37/32) and others (n = 36/4). Pathogens were eradicated from 172 (96%) of 180 bacteriologically evaluable children. Overall 122 (98%) of 125 isolates of S. pneumoniae were eradicated, including 31 (91%) of 34 PRSP isolates (penicillin MICs 2 to 4 micrograms/ml). Seventy-eight (94%) of 83 isolates of H. influenzae were eradicated. Symptoms and otoscopic signs of acute inflammation were completely resolved or improved on Days 12 to 15 in 263 (89%) of 295 clinically evaluable children with bacteriologically documented AOM. CONCLUSIONS: On the basis of bacteriologic outcome on Days 4 to 6 and clinical outcome on Days 12 to 15, we found that high dose amoxicillin/clavulanate (90/6.4 mg/kg/day) was highly efficacious in children with AOM, including those most likely to fail treatment, namely children < 24 months of age and those with infectious caused by PRSP.

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.

Early detection of sequela-prone osteomyelitis in children with use of simple clinical and laboratory criteria.

To determine which clinical or laboratory criteria best reflected the prognosis for 83 children with acute hematogenous osteomyelitis (AHO), they were compared with outcomes after a follow-up of at least 2 months (for 78%, > or = 6 months). Twenty-eight children (34%) developed sequelae. They had higher serum C-reactive protein (CRP) concentrations (days 1-6 of treatment; P = .0004 to .0001) and higher clinical scores (P = .0001) than did patients who had an uneventful recovery. The frequency of sequelae increased from 3% to 73% (P = .0001) when CRP concentrations exceeded the defined cutoff limits and the clinical scores were > or = 1. Age, the duration of symptoms at diagnosis, and the type and duration of intravenous antimicrobial therapy or surgical management did not differ (P > .05) between children with and without sequelae. Both CRP determinations and clinical evaluations with use of a scoring system enable early detection of sequela-prone AHO in children and are most accurate when used together.

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.

Paragonimus mexicanus pericarditis: report of two cases and review of the literature.

The cases of two Costa Rican children with pericarditis due to Paragonimus mexicanus are reported. Clinical, epidemiological and laboratory tests are consistent with the disease. Treatment with praziquantel and bitheonol was associated with clinical cure. A review of the literature and a suggested table of diagnostic criteria are included.

Serial serum C-reactive protein to monitor recovery from acute hematogenous osteomyelitis in children.

Serial C-reactive protein (CRP) and erythrocyte sedimentation rate determinations were compared with clinical course and outcome at 1 to 2 months in 63 children with acute hematogenous osteomyelitis. High CRP values (163 +/- 108 mg/liter) on admission began to descend after the second day of treatment. From the fourth day on higher (P = 0.03 to P = 0.0001) CRP values distinguished a complicated from an uneventful course of acute hematogenous osteomyelitis and the patients symptomatic at follow-up (P = 0.003 to P = 0.0001) from asymptomatic ones. Children who developed extensive radiographic changes had elevated CRP values for a longer time (32 +/- 13 days) than children with typical changes (11 +/- 6 days, P = 0.0001). Erythrocyte sedimentation rates did not identify the type of clinical course but higher values on Days 4 to 7 distinguished children symptomatic at follow-up (P = 0.02) from asymptomatic ones. Monitoring serial CRP values can alert the physician to complications and predict outcome earlier than clinical signs or roentgenograms.

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.

Prevention of rheumatic fever in Costa Rica.

During the beginning of the 1970s, major changes occurred in Costa Rica in the treatment of streptococcal throat infections. Because of poor compliance with regimens using orally administered agents, intramuscular administration of benzathine penicillin was selected as the standard treatment and throat cultures were eliminated as a prerequisite for prescribing antibiotics. A decline in the incidence of rheumatic fever then occurred. We believe that similar health intervention could be applied in other developing countries.