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Pediatric acute respiratory tract infections (ARTIs) are a leading cause of morbidity and mortality. The objectives of this study were to describe the epidemiology of polymicrobial ARTI in a hospital-based pediatric population and to investigate the association of polymicrobial infection and severity of illness. We conducted a retrospective study of 559 archived respiratory specimens from 421 children under the age of 10 years collected from March 28, 2008 through June 30, 2009 and stored by the University of Iowa Hospital and Clinics Clinical Microbiology Laboratory. Specimens were tested by immunofluorescence assay and/or viral culture at the time of collection (influenza A and B, parainfluenza [PIV] 1-3, respiratory syncytial virus [RSV], adenovirus [Ad]) and uniformly by RT-PCR (human metapneumovirus [hMPV], rhinovirus [HRV], human bocavirus [HBoV]) and PCR (Ad) for the current study. Demographic and clinical data were abstracted from electronic medical records. Results from this study suggest that polymicrobial respiratory tract infections are common in this population. A virus was identified in 61.3% of 349 respiratory specimens from children with confirmed or suspected ARTI. HRV (27.5%), RSV (18.9%), HBoV (8.3%), hMPV (7.7%), and PIV (6.6%) were the most common viruses detected. A viral coinfection was identified in 21.5% of the 214 virus-positive specimens and was most often detected for Ad (53.3% of 15 Ad-positive specimens), HBoV (51.7% of 29 HBoV-positive specimens), PIV (43.5% of 23 PIV-positive specimens), HRV (35.4% of 96 HRV-positive specimens), and RSV (34.8% of 66 RSV-positive specimens). Among the 46 specimens with dual or triple viral coinfections detected, the most frequent virus-virus combination was HRV-RSV (n=12). We hypothesized that certain host-specific risk factors were associated with the likelihood of viral coinfection. While none of the covariates in the final model were significant, the results were suggestive. Male gender (OR 1.70, 95% CI 0.83-3.46), age between 6 months to 1 year (as compared to children less than 6 months old, OR 2.15, 95% CI 0.75-6.19), and history of any chronic condition that may result in immunosuppression (OR 2.05, 95% CI 0.99-4.23) were each associated with increased odds of viral coinfection (p > 0.05). We also hypothesized that children with coinfections would be more likely to have severe ARTI. Children with viral-bacterial coinfection, as compared to children with viral mono-infection, were more likely to be admitted to an intensive care unit (OR 6.00, 95% CI 2.51-14.33) even after controlling for age, history of prematurity, urban/rural residence, and leukocytosis. This study will inform medical and public health professionals with regard to the epidemiology of polymicrobial infections and their potential importance as a cause of severe acute respiratory tract infection in children. Furthermore, results of this study may contribute to the ongoing discussion of the importance of diagnostic ability to reliably detect multiple concurrent pathogens in a single individual.

Background: Persistent cough following an acute respiratory tract infection is a challenging and frequently encountered problem in primary care. Mycoplasma pneumoniae (M. pneumoniae) and Bordetella pertussis (pertussis) particularly predispose patients to persistent cough. Whilst the incidence of M. pneumoniae is highest in children, pertussis may also occur in adults. Method: Four studies were conducted for this thesis. First, a systematic review to assess the diagnostic accuracy of symptoms and signs in the clinical recognition of M. pneumoniae. Second, a retrospective analysis of a cohort of children with persistent cough to assess the prognostic value of diagnosing M. pneumoniae. Third, a prospective cohort study to estimate the prevalence of M. pneumoniae and pertussis in children with persistent cough following recent changes in vaccination policy. Fourth, a double-blind randomised placebo-controlled trial to determine the effectiveness of montelukast in the treatment of persistent cough and pertussis-induced cough in adults. Results: M. pneumoniae and pertussis can each be found in one-sixth of children who present in primary care with persistent cough. Although coverage with the preschool pertussis booster vaccine is high, its efficacy wanes rapidly, with the likelihood of pertussis increasing by 30% per year after vaccination. Montelukast is not an effective treatment for persistent cough, but may be an effective treatment for pertussis-induced cough. Median duration of cough in children with M. pneumoniae is only one-third of that in children with pertussis (39 days versus 118 days). However, the diagnostic accuracy of symptoms and signs in the clinical recognition of M. pneumoniae is limited. Since M. pneumoniae occurs in cyclical epidemics, clinicians should consider current prevalence of M. pneumoniae when making a clinical diagnosis. Conclusions: Diagnosing M. pneumoniae and pertussis can help clinicians give patients an explanation for their cough and inform them about its likely prognosis. At the moment, clinicians should adopt a conservative approach to managing postinfectious persistent cough. A further trial is needed to assess the efficacy of montelukast for the treatment of pertussis-induced cough.

A dificuldade de realização de estudos clínicos com a população pediátrica favorece a prescrição off-label de medicamentos. Paralelamente, existe uma grande diversidade de fontes de informações sobre medicamentos disponíveis para consulta e diferentes formas de expressar doses para a pediatria, podendo resultar em padrões variados no uso de medicamentos. Este estudo avaliou a concordância de fontes de informação, em nível nacional e internacional, que orientam a prescrição pediátrica de antimicrobianos para faringotonsilite, otite média aguda (OMA) e rinossinusite, em relação ao fármaco de escolha, à posologia e aos tipos de referências utilizadas para sua elaboração. Foram selecionados documentos de entidades brasileiras e estrangeiras e as bulas dos medicamentos neles mencionados, totalizando 23 documentos diferentes para as três doenças avaliadas. A classe das penicilinas foi prevalente como terapia de primeira escolha nas três doenças estudadas, contudo houve grande variação nas doses indicadas e no modo como elas são expressas. A idade mínima para uso foi informada em 51,2% das fontes, sendo menos recorrente nas fontes nacionais. A duração do tratamento esteve presente em 66,7% dos fármacos indicados nas fontes. De forma geral, as fontes analisadas para as três doenças avaliadas citam principalmente referências classificadas como artigos de revisão e estudos experimentais, seguidos dos formulários e listas oficiais e consensos, diretrizes e manuais para embasar seus dados. Os resultados encontrados neste estudo reforçam a necessidade de estimular a realização de ensaios clínicos e/ ou estudos de farmacometria para a definição de doses de antimicrobianos para a pediatria, assim como, a harmonização das informações disponibilizadas para orientar a prescrição. / The difficulty of conducting clinical studies with the pediatric population favors off-label prescribing. At the same time, there is easy access to a great diversity of sources of information about drugs and different ways of expressing pediatric doses. These factors have impact on drug prescription and may result in varying standards in the use of medications. The present study assessed, at national and international levels, the agreement of information sources that guide pediatric prescription of antimicrobials for pharyngotonsillitis, acute otitis media (AOM) and rhinosinusitis, in relation to the drug of choice, dosage and types of references used in its preparation. Documents from Brazilian and international entities and the package inserts of the medications mentioned in these documents were selected. To three diseases, was analyzed 23 differents documents. The penicillin class was prevalent as first-line therapy in the three diseases investigated. However, there was great variation in the doses indicated and in the way they are expressed. The minimum age for use was reported in only 51,2% of the sources, being less recurrent in the national sources. Duration of treatment was present in 66,7% of the drugs indicated in the sources. In general, the sources analyzed for the three disorders investigated most often cite references classified as review articles and experimental studies, followed by formularies and official lists and consensus, guidelines and manuals to support their data. The results obtained reinforce the need to encourage clinical trials and/or pharmacometrics studies for establishing dosing recommendations of antimicrobials for pediatric patients, as well as to harmonize the information provided to guide prescriptions.

Nepagrįstas antibiotikų vartojimas gydant ūmine viršutinių kvėpavimo takų infekcija (ŪVKTI) sergančius pacientus ne tik sąlygoja atsparių antimikrobiniams vaistams bakterijų padermių vystymąsi, bet ir didina nepageidaujamo vaistų poveikio dažnį bei išlaidų sveikatos priežiūrai kaštus. Lietuvoje iki šiol nebuvo analizuotos priežastys, lemiančios gydytojų sprendimą skirti bei pacientų norą sulaukti antibiotikų ŪVKTI gydymui. Darbo tikslas – nustatyti ir įvertinti antibiotikų vartojimo ŪVKTI gydymui dažnį ir priežastis Kauno apskrities PSP įstaigose. Darbo uždaviniai - nustatyti antibiotikų skyrimo ŪVKTI gydymui dažnį ir priklausomybę nuo ŪVKTI išraiškos; įvertinti paciento lūkesčius sulaukti antibiotikų ŪVKTI gydymui bei jų ryšį su gydytojo sprendimu skirti antibiotikų ŪVKTI gydymui; įvertinti ligos eigos, gydytojo amžiaus, specialybės bei darbo aplinkos ir sprendimo skirti antibiotikų ŪVKTI sergantiems pacientams sąsajas. Išvados: Sulaukti recepto antibiotikams tikisi trečdalis į PSP įstaigą atvykusių pacientų. Pacientų lūkestis gauti antibiotikų ŪVKTI gydymui susijęs su gydytojo sprendimu skirti šių vaistų. Kauno apskrities PSP įstaigų gydytojai antibiotikų ŪVKTI gydymui skiria 40,2 proc. atvejų. Nepagrįstai daug (32,8 proc.) antibiotikų skiriama “paprastam peršalimui” gydyti. Persikvalifikavę į šeimos gydytojus terapeutai bei vyresnio amžiaus gydytojai antibiotikų ŪVKTI gydymui skiria dažniau lyginant su stacionarią rezidentūrą baigusiais bei jaunesniais šeimos gydytojais. / Most commonly AURTI are caused by viruses, and since antibiotics are ineffective against viral infections, researchers in a number of countries have concluded that the rates of antibiotic prescription for AURTI are unjustifiably high. The aim of the study was to determine and evaluate the reasons and rate of antibiotic use for the treatment of AURTI in primary healthcare units of Kaunas County. The objectives of the study were to determine the rate of prescribing antibiotics for AURTI; to evaluate the patients’ expectations to receive antibiotics for AURTI and to assess the relationship of these expectations with the physicians’ decision to prescribe antibiotics for this disorder; to evaluate the associations of the phy¬sician’s age, specialty and working environment with the decision to prescribe antibiotics for patients with AURTI. Conclusions: One-third of patients who visited PHC institutions expected to receive prescriptions for antibiotics. The patients’ expectations to receive antibiotics for the treatment of AURTI was related to the physicians’ decision to prescribe antibiotics. Physicians of PHC institutions of Kaunas County prescribe antibiotics for AURTI in 40.2% of cases. With unjustified rate (32.8%) antibiotics are prescribed for “common cold”. Internists who had re-qualified as family physicians and older physi¬cians prescribed antibiotics more frequently, compared to those who had comple¬ted full-time residency in family medicine and younger physicians.

Respiratory Syncytial Virus (RSV) infection is common among young children. Congenital Heart Disease (CHD) is a risk factor of severe illness and hospitalization. Palivizumab prophylaxis reduces the severity of RSV infection and reduces the risk of hospitalization for children at high risk of severe illness, such as children born premature or with CHD. The aim of this thesis was to evaluate compliance with national guidelines for prophylactic treatment and to study the Relative Risk (RR) of hospitalization due to RSV and unspecified Respiratory Tract Infection (RTI) for children with CHD. In a prospective study, questionnaires were sent to all paediatric cardiology centres in Sweden with questions about prophylactic treatment. Hospitalization rates were retrieved from the national inpatient registry. Heart defects were grouped according to type and the relative risk of hospitalization was calculated for each group and for summer and winter seasons. Half of the patients received prophylactic treatment later than recommended in the guidelines. The risk of hospitalization due to RSV infection was increased (RR=2.06 95% CI 1.6-2.6; p < 0.0001) for children with CHD compared to children without CHD. The RR of hospitalization was also increased for all CHD subgroups, and was further increased during summer for children with the more severe CHD. We conclude that guidelines for prophylactic treatment were not followed and that the risk of hospitalization due to RSV and unspecified RTI was increased for all subgroups of CHD. The risk was increased both during winter and summer and we therefore argue that information to health personnel and parents should include that the risk of severe RTI is present all year round for children with CHD. / Respiratoriskt syncytialvirus (RSV) är det vanligaste förkylningsviruset och de allra flesta barn drabbas före två års ålder. RSV kan leda till allvarlig luftvägsinfektion hos alla barn, men speciellt hos dem med medfött hjärtfel. Någon botande läkemedelsbehandling finns inte för RSV, utan de medicinska insatserna får inriktas mot att mildra sjukdomsförloppet och för svårt sjuka barn krävs sjukhusvård för att exempelvis erhålla syrgasbehandling. Det finns inget vaccin mot RSV, men barn som riskerar att bli svårt sjuka kan behandlas profylaktiskt med en monoklonal antikropp (Palivizumab) som ges som injektion en gång per månad under vintersäsong. Vissa barn med svårt hjärtfel får denna profylaktiska behandling enligt nationella riktlinjer. Vår första studie visade att ungefär hälften av barnen med medfött hjärtfel, aktuella för profylax mot RSV, fick behandlingen senare än vad de nationella riktlinjerna rekommenderade. Denna studie genomfördes via en enkät till alla landets barnkliniker under två vintersäsonger. Vi såg även att något fler barn än förväntat (4.6%) fick RSV-infektion trots profylaktisk behandling och för cirka en tredjedel av dessa barn fördröjdes tiden till hjärtoperation. Behovet av sjukhusvård kan användas som mått på hur svårt ett sjukdomsförlopp är, och baserat på Socialstyrelsens slutenvårdsregister studerade vi alla barn under två års ålder och fann att den relativa risken för sjukhusvård på grund av RSV var högre för barn med hjärtfel än för barn utan hjärtfel (RR=2.06 95% CI 1.6-2.6; p < 0.0001). I vår andra studie, baserad på slutenvårdsregistret, beräknade vi den relativa risken för sjukhusvård på grund av RSV, för barn med olika former av hjärtfel och uppdelat i sommar- och vintersäsong. Risken för sjukhusvård var ökad för alla barn oavsett typ av hjärtfel, och detta gällde såväl under vintern som under sommaren. Barn med de allvarligaste formerna av hjärtfel hade högre risk för sjukhusvård under sommaren jämfört med deras risk under vintern, medan barn med vad som anses vara lättare hjärtfel hade ökad risk för sjukhusvård under hela året, utan någon större skillnad i risk mellan vinter och sommar. Att barn med hjärtfel riskerar att bli svårt sjuka i RSV är väl känt, men våra resultat visar att denna risk även existerar under sommarhalvåret, då det inte är RSV-säsong och då profylax inte ges. Vi fann också att barn med vad som anses vara lättare hjärtfel löper lika stor risk att drabbas av svårare sjukdomsförlopp med sjukhusvård under vintern, som barn med svårare hjärtfel. Att denna information sprids till såväl sjukvårdspersonal som arbetar med denna patientgrupp som till föräldrar med hjärtsjuka barn är viktigt, för att belysa att även dessa barn behöver skyddas, och detta inte bara under vintern och RSV-säsongen.

A dificuldade de realização de estudos clínicos com a população pediátrica favorece a prescrição off-label de medicamentos. Paralelamente, existe uma grande diversidade de fontes de informações sobre medicamentos disponíveis para consulta e diferentes formas de expressar doses para a pediatria, podendo resultar em padrões variados no uso de medicamentos. Este estudo avaliou a concordância de fontes de informação, em nível nacional e internacional, que orientam a prescrição pediátrica de antimicrobianos para faringotonsilite, otite média aguda (OMA) e rinossinusite, em relação ao fármaco de escolha, à posologia e aos tipos de referências utilizadas para sua elaboração. Foram selecionados documentos de entidades brasileiras e estrangeiras e as bulas dos medicamentos neles mencionados, totalizando 23 documentos diferentes para as três doenças avaliadas. A classe das penicilinas foi prevalente como terapia de primeira escolha nas três doenças estudadas, contudo houve grande variação nas doses indicadas e no modo como elas são expressas. A idade mínima para uso foi informada em 51,2% das fontes, sendo menos recorrente nas fontes nacionais. A duração do tratamento esteve presente em 66,7% dos fármacos indicados nas fontes. De forma geral, as fontes analisadas para as três doenças avaliadas citam principalmente referências classificadas como artigos de revisão e estudos experimentais, seguidos dos formulários e listas oficiais e consensos, diretrizes e manuais para embasar seus dados. Os resultados encontrados neste estudo reforçam a necessidade de estimular a realização de ensaios clínicos e/ ou estudos de farmacometria para a definição de doses de antimicrobianos para a pediatria, assim como, a harmonização das informações disponibilizadas para orientar a prescrição. / The difficulty of conducting clinical studies with the pediatric population favors off-label prescribing. At the same time, there is easy access to a great diversity of sources of information about drugs and different ways of expressing pediatric doses. These factors have impact on drug prescription and may result in varying standards in the use of medications. The present study assessed, at national and international levels, the agreement of information sources that guide pediatric prescription of antimicrobials for pharyngotonsillitis, acute otitis media (AOM) and rhinosinusitis, in relation to the drug of choice, dosage and types of references used in its preparation. Documents from Brazilian and international entities and the package inserts of the medications mentioned in these documents were selected. To three diseases, was analyzed 23 differents documents. The penicillin class was prevalent as first-line therapy in the three diseases investigated. However, there was great variation in the doses indicated and in the way they are expressed. The minimum age for use was reported in only 51,2% of the sources, being less recurrent in the national sources. Duration of treatment was present in 66,7% of the drugs indicated in the sources. In general, the sources analyzed for the three disorders investigated most often cite references classified as review articles and experimental studies, followed by formularies and official lists and consensus, guidelines and manuals to support their data. The results obtained reinforce the need to encourage clinical trials and/or pharmacometrics studies for establishing dosing recommendations of antimicrobials for pediatric patients, as well as to harmonize the information provided to guide prescriptions.

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2013-04-16T19:40:46Z No. of bitstreams: 1 raquel_simbalista_de queiroz. Aspectos da admissao. 2010.pdf: 39174617 bytes, checksum: e35efd5722282aa850fa314a2345a654 (MD5) / Made available in DSpace on 2013-04-16T19:40:46Z (GMT). No. of bitstreams: 1 raquel_simbalista_de queiroz. Aspectos da admissao. 2010.pdf: 39174617 bytes, checksum: e35efd5722282aa850fa314a2345a654 (MD5) Previous issue date: 2010 / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, Bahia, Brasil / Fundação OSwaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, Bahia, Brasil / A pneumonia na infância permanece um assunto relevante, tendo em vista a sua elevada taxa de mortalidade mundial, principalmente nos países em desenvolvimento. Objetivo: Descrever o resultado da hospitalização de crianças internadas com suspeita diagnostica de pneumonia. Desenho do estudo: Coorte retrospectiva. Material e métodos: Foi realizado acompanhamento retrospectivo de pacientes internados com suspeita de pneumonia em um centro pediátrico, de outubro de 2002 a outubro de 2005. A partir dos prontuários médicos, dados demográficos, de história clínica, do exame físico, do tratamento, da evolução e do desfecho foram coletados e registrados em formulário específico para o estudo. Todos os casos incluídos tiveram as radiografias de tórax avaliadas por radiologista cego às informações clínicas, com o objetivo de definir a presença ou não de infiltrado pulmonar e avaliar a presença de alterações radiológicas outras. A população do estudo foi alocada -“m quatro grupos diferente? para que pudessem ter suas variáveis comparadas entre pacientes com características semelhantes. Resultados: No grupo das crianças > 2 meses de idade, internadas com diagnóstico clínico-radiológico de pneumonia e tratadas com penicilina cristalina, as freqüências de febre (46,4% vs. 26,3%, /’=0,002), taquipnéia (73,6% vs. 59,4%, ^=0,003), tiragem subcostal (29,4% vs. 12,7%, /’<0,001) e aleteo nasal (10,2% vs. 1,6%, 7^=0,001) diminuíram de forma significante entre a admissão e o primeiro dia de tratamento. A penicilina foi substituída após 48 horas por outros antibióticos em 28 (18,2%) dos pacientes, nos quais houve redução significante da taquipnéia entre o primeiro e o segundo dia de tratamento (86,4% ví. 50,0%, /*=0,008). Nas crianças com idade < 2 meses, internadas com diagnóstico clínico ou clínico-radiológico de pneumonia e tratadas com antibióticos diversos, o esquema antibiótico mais utilizado foi a monoterapia com penicilina cristalina e derivados ou associação com cefalosporinas (68,9%). A antibioticoterapia inicial foi modificada em 8,9% dos casos, tendo 62,5% e 58,5% recebido alta após cura ou melhora, respectivamente. Entre aqueles que não modificaram a terapêutica inicial, 58,5% foram classificados como cura e 41,5% como melhora. Nas crianças com idade > 2 meses, com diagnóstico clínico ou clínico-radiológico de pneumonia, tratadas com antibióticos diversos, excluindo-se aquelas pertencentes aos outros grupos, a escolha inicial por penicilina cristalina foi mais frequente. Com relação ao desfecho, 191 (64,1%) dos pacientes receberam alta após cura e 107 (35,2%) após melhora clínica. 13 Finalmente, entre as crianças com idade > 2 meses internadas com diagnóstico clínico ou clínico-radiológico de pneumonia tratadas com penicilina cristalina, o que incluiu aquelas do primeiro grupo, todas foram consideradas curadas (72,6%) ou com melhora clínica (27,4%) no momento da alta hospitalar. A freqüência de cura foi maior entre os pacientes que não modificaram a antibioticoterapia inicial (p<0,001). Conclusões principais: Pôde-se observar que em todos os grupos, indistintamente, a antibioticoterapia concordante permaneceu como uma conduta fundamental para o tratamento da pneumonia. Além disso, a aderência à antibioticoterapia empírica conforme as diretrizes foi considerável, principalmente quando o diagnóstico clínico foi confirmado pelo radiológico, sendo essa conduta uma das chaves para o tratamento eficaz da pneumonia na faixa etária pediátrica. / Childhood pneumonia remains a relevant issue, due to its mortality rates worldwide, especially in developing countries. Objective: The present study has the main purpose to describe the outcome among children hospitalized with suspected pneumonia. Design: Retrospective cohort. Methods: This is a retrospective review of suspected cases of pneumonia in children hospitalized in a pediatric center of Salvador, North-east Brazil, from October/2002 to October/2005. A standardized form containing data on demographics and clinical history, physical examination, treatment, evolution and outcome during the first five or seven days of hospitalization was filled in for each patient, according to medical charts. The radiological reading was performed by a pediatric radiologist blind to clinical information, to define the presence of pulmonary infiltrate or other findings. The study population was allocated in four distinct groups, to compare each group with homogeneous aspects. Results: Among the group of children aged ¿ 2 months hospitalized wi" radiographically diagnosed pneumonia, treated with intravenous aqueous penicillin G, fever (46.4% vs. 26.3%, P=0.002), tachypnea (73.6% v^. 59.4%, P=0.003), chest indrawing (29.4% V5. 12.7%, /'<0.001) and nasal flaring (10.2% vs. 1.6%, F-O.OOl) frequencies significantly decreased from admission to first day of treatment. Penicillin was substituted by other antibiotics in 28 (18.2%) patients in whom the sole significant decrease was on tachypnea frequency from first to second day of treatment (86.4% vs. 50.0%, P=0.008). Among children aged < 2 months hospitalized with suspected pneumonia, treated with several antibiotic schemes, the most frequent first antibiotic scheme were penicillin and derivates alone or associated with cephalosporines (68.9%). The antibiotic had been changed after 48 hours in 8.9% of cases during hospitalization, and 62.5% were discharged after cure, against 37.5% improvements. From those who did not switched therapy, 58.5% were cured and 41.5% improved. In the group of children aged > 2 months old hospitalized with suspected pneumonia, excluding those of the other three groups, the choice for penicillin G had higher frequencies than the other schemes registered, among all age groups. According to outcome, 191 (64.1%) those children > 2 months old hospitalized with suspected pneumonia, treated with intravenous aqueous penicillin G, what includes children from the first group, all were considered improved (27.4%) or cured (72.6%) at the time of hospital discharge, and there was significantly more cure among those who 15 did not switched therapy (p<0.001). Main conclusions: From the aforementioned data, it is possible to observe that guideline-concordant empiric antibiotic remains an important procedure to an effective treatment of pneumonia among children of all age groups. Besides, the adherence of empiric antibiotic therapy was good among physicians in our study, especially when there was concordance between the clinical and radiological diagnosis; and this approach is one of the keys to an effective treatment of childhood pneumonia.