Usefulness of betalactam therapy for community-acquired pneumonia in the era of drug-resistant Streptococcus pneumoniae: a randomized study of amoxicillin-clavulanate and ceftriaxone

Empirical antibiotic therapy of community-acquired pneumonia (CAP) has been complicated by the worldwide emergence of penicillin resistance among Streptococcus pneumoniae. The impact of this resistance on the outcome of patients hospitalized for CAP, empirically treated with betalactams, has not been evaluated in a randomized study. We conducted a prospective, randomized trial to assess the efficacy of amoxicillin-clavulanate (2 g/200 mg/8 hr) and ceftriaxone (1 g/24 hr) in a cohort of patients hospitalized for moderate-to-severe CAP. Three-hundred seventy-eight patients were randomized to receive amoxicillin-clavulanate (184 patients) or ceftriaxone (194 patients). Efficacy was assessed on Day 2, after completion of therapy and at long term follow-up. There were no significant differences in outcomes between treatment groups, both in intention-to-treat and per-protocol analysis. Overall mortality was 10.3% for amoxicillin-clavulanate and 8.8% for ceftriaxone (NS). There were 116 evaluable patients with proven pneumococcal pneumonia. Rates of high-level penicillin resistance (MIC of penicillin ≥2 µg/mL) were similar in the two groups (8.2 and 10.2%). Clinical efficacy at the end of therapy was 90.6% for amoxicillin-clavulanate and 88.9% for ceftriaxone (95% C.I. of the difference: -9.3 to +12.7%). No differences in outcomes were attributable to differences in penicillin susceptibility of pneumococcal strains. Sequential i.v./oral amoxicillin-clavulanate and parenteral ceftriaxone were equally safe and effective for the empirical treatment of acute bacterial pneumonia, including penicillin and cephalosporin-resistant pneumococcal pneumonia. The use of appropriate betalactams in patients with penumococcal pneumonia and in the overall CAP population, is reliable at the current level of resistance

Clinical features for diagnosis of pneumonia in children younger than 5 years: a systematic review and meta-analysis.

BACKGROUND: Pneumonia is the biggest cause of deaths in young children in developing countries, but early diagnosis and intervention can effectively reduce mortality. We aimed to assess the diagnostic value of clinical signs and symptoms to identify radiological pneumonia in children younger than 5 years and to review the accuracy of WHO criteria for diagnosis of clinical pneumonia. METHODS: We searched Medline (PubMed), Embase (Ovid), the Cochrane Database of Systematic Reviews, and reference lists of relevant studies, without date restrictions, to identify articles assessing clinical predictors of radiological pneumonia in children. Selection was based on: design (diagnostic accuracy studies), target disease (pneumonia), participants (children aged <5 years), setting (ambulatory or hospital care), index test (clinical features), and reference standard (chest radiography). Quality assessment was based on the 2011 Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) criteria. For each index test, we calculated sensitivity and specificity and, when the tests were assessed in four or more studies, calculated pooled estimates with use of bivariate model and hierarchical summary receiver operation characteristics plots for meta-analysis. FINDINGS: We included 18 articles in our analysis. WHO-approved signs age-related fast breathing (six studies; pooled sensitivity 0·62, 95% CI 0·26-0·89; specificity 0·59, 0·29-0·84) and lower chest wall indrawing (four studies; 0·48, 0·16-0·82; 0·72, 0·47-0·89) showed poor diagnostic performance in the meta-analysis. Features with the highest pooled positive likelihood ratios were respiratory rate higher than 50 breaths per min (1·90, 1·45-2·48), grunting (1·78, 1·10-2·88), chest indrawing (1·76, 0·86-3·58), and nasal flaring (1·75, 1·20-2·56). Features with the lowest pooled negative likelihood ratio were cough (0·30, 0·09-0·96), history of fever (0·53, 0·41-0·69), and respiratory rate higher than 40 breaths per min (0·43, 0·23-0·83). INTERPRETATION: Not one clinical feature was sufficient to diagnose pneumonia definitively. Combination of clinical features in a decision tree might improve diagnostic performance, but the addition of new point-of-care tests for diagnosis of bacterial pneumonia would help to attain an acceptable level of accuracy. FUNDING: Swiss National Science Foundation.

Severe pneumonia due to Parachlamydia acanthamoebae following intranasal inoculation: a mice model.

Parachlamydia acanthamoebae is an obligate intracellular bacterium naturally infecting free-living amoebae. The role of this bacterium as an agent of pneumonia is suggested by sero-epidemiological studies and molecular surveys. Furthermore, P. acanthamoebae may escape macrophages microbicidal effectors. Recently, we demonstrated that intratracheal inoculation of P. acanthamoebae induced pneumonia in 100% of infected mice. However, the intratracheal route of infection is not the natural way of infection and we therefore developed an intranasal murine model. Mice inoculated with P. acanthamoebae by intranasal inoculation lost 18% of their weight up to 8 days post-inoculation. All mice presented histological signs of pneumonia at day 2, 4, 7, and 10 post-inoculation, whereas no control mice harboured signs of pneumonia. A 5-fold increase in bacterial load was observed from day 0 to day 4 post-inoculation. Lungs of inoculated mice were positive by Parachlamydia-specific immunohistochemistry 4 days post-inoculation, and P. acanthamoebae were localized within macrophages. Thus, we demonstrated that P. acanthamoebae induce a severe pneumonia in mice. This animal model (i) further supports the role of P. acanthamoebae as an agent of pneumonia, confirming the third Koch postulate, and (ii) identified alveolar macrophages as one of the initial cells where P. acanthamoebae is localized following infection.

Community-acquired pneumonia in adult patients with special reference to rapid methods for etiological diagnosis

Aikuispotilaan kotisyntyisen keuhkokuumeen etiologinen diagnostiikka mikrobiologisilla pikamenetelmillä Tausta. Keuhkokuume on vakava sairaus, johon sairastuu Suomessa vuosittain n. 60 000 aikuista. Huolimatta siitä, että taudin hoito on kehittynyt, siihen liittyy yhä merkittävä, 6-15%:n kuolleisuus. Alahengitystieinfektion aiheuttajamikrobien tunnistaminen on myös edelleen haasteellista. Tavoitteet. Tämän työn tavoitteena oli tutkia Turun yliopistollisessa keskussairaalassa hoidettujen aikuispotilaiden keuhkokuumeen etiologiaa sekä selvittää uusien mikrobiologisten pikamenetelmi¬en hyödyllisyyttä taudinaiheuttajan toteamisessa. Aineisto. Osatöiden I ja III aineisto koostui 384 Turun yliopistollisen keskussairaalaan infektio-osastolla hoidetusta keuhkokuumepotilaasta. Osatyössä I tutkittiin keuhkokuumeen aiheuttaja¬mikrobeja käyttämällä perinteisten menetelmien lisäksi antigeeniosoitukseen ja PCR-tekniikkaan perustuvia pikamenetelmiä. Osatyö II käsitti 231 potilaasta koostuvan alaryhmän, jossa tutkittiin potilaiden nielun limanäytteestä rinovirusten ja enterovirusten esiintyvyyttä. Osatyössä III potilailta tutkittiin plasman C-reaktiivisen proteiinin (CRP) pitoisuus ensimmäisten viiden sairaalahoitopäi¬vän aikana. Laajoja tilastotieteellisiä analyysejä käyttämällä selvitettiin CRP:n käyttökelpoisuutta sairauden vaikeusasteen arvioinnissa ja komplikaatioiden kehittymisen ennustamisessa. Osatyössä IV 68 keuhkokuumepotilaan sairaalaan tulovaiheessa otetuista näytteistä määritettiin neutrofiilien pintareseptorien ekspressio. Osatyössä V analysoitiin sisätautien vuodeosastoilla vuosina 1996-2000 keuhkokuumepotilaille tehtyjen keuhkohuuhtelunäytteiden laboratoriotutkimustulokset. Tulokset. Keuhkokuumeen aiheuttaja löytyi 209 potilaalta, aiheuttajamikrobeja löydettiin kaikkiaan 230. Näistä aiheuttajista 135 (58.7%) löydettiin antigeenin osoituksella tai PCR-menetelmillä. Suu¬rin osa, 95 (70.4%), todettiin pelkästään kyseisillä pikamenetelmillä. Respiratorinen virus todettiin antigeeniosoituksella 11.1% keuhkokuumepotilaalla. Eniten respiratorisia viruksia löytyi vakavaa keuhkokuumetta sairastavilta potilailta (20.3%). 231 keuhkokuumepotilaan alaryhmässä todettiin PCR-menetelmällä picornavirus 19 (8.2%) potilaalla. Respiratorinen virus löytyi tässä potilasryh¬mässä kaiken kaikkiaan 47 (20%) potilaalta. Näistä 17:llä (36%) löytyi samanaikaisesti bakteerin aiheuttama infektio. CRP-tasot olivat sairaalaan tulovaiheessa merkitsevästi korkeammat vakavaa keuhkokuumetta (PSI-luokat III-V) sairastavilla potilailla kuin lievää keuhkokuumetta (PSI-luokat I-II) sairastavilla potilailla (p <0.001). Yli 100 mg/l oleva CRP-taso neljän päivän kuluttua sairaa¬laan tulosta ennusti keuhkokuumeen komplikaatiota tai huonoa hoitovastetta. Neutrofiilien komple¬menttireseptorin ekspressio oli pneumokokin aiheuttamaa keuhkokuumetta sairastavilla merkitse¬västi korkeampi kuin influenssan aiheuttamaa keuhkokuumetta sairastavilla. BAL-näytteistä vain yhdessä 71:stä (1.3%) todettiin diagnostinen bakteerikasvu kvantitatiivisessa viljelyssä. Uusilla menetelmilläkin keuhkokuumeen aiheuttaja löytyi vain 9.8% BAL-näytteistä. Päätelmät. Uusilla antigeeniosoitus- ja PCR-menetelmillä keuhkokuumeen etiologia voidaan saada selvitettyä nopeasti. Lisäksi näitä menetelmiä käyttämällä taudin aiheuttajamikrobi löytyi huomattavasti suuremmalta osalta potilaista kuin pelkästään tavanomaisia menetelmiä käyttämällä. Pikamenetelmien hyödyllisyys vaihteli taudin vaikeusasteen mukaan. Respiratorinen virus löytyi huomattavan usein keuhkokuumetta sairastavilta potilailta, ja näiden potilaiden taudinkuva oli usein vaikea. Tulovaiheen korkeaa CRP-tasoa voidaan käyttää lisäkeinona arvioitaessa keuhkokuumeen vaikeutta. CRP on erityisen hyödyllinen arvioitaessa hoitovastetta ja riskiä komplikaatioiden ke¬hittymiseen. Neutrofiilien komplementtireseptorin ekspression tutkiminen näyttää lupaavalta pi¬kamenetelmältä erottamaan bakteerien ja virusten aiheuttamat taudit toisistaan. Antimikrobihoitoa saavilla potilailla BAL-tutkimuksen löydökset olivat vähäiset ja vaikuttivat hoitoon vain harvoin.

Procalcitonin is useful in identifying bacteraemia among children with pneumonia

Empirical antibiotic use is prescribed in managing children with pneumonia worldwide. We assessed the usefulness of procalcitonin (PCT) and interferon-alpha (IFN-alpha) in differentiating viral from bacterial pneumonia. Among 159 hospitalized children, pneumonia was diagnosed based on clinical complaints plus pulmonary infiltrate. Aetiology was investigated for 9 viruses and 4 atypical and 3 typical bacteria. PCT and IFN-alpha were measured in the serum sample collected on admission. Eight patients had bacteraemic infections, 38 had non-bacteraemic typical infections, and 19 patients had atypical bacterial infections. Viral and unknown aetiology was established in 57 (36%) and 34 (21%) cases, respectively. Three patients with bacterial infection without collected blood culture were excluded. IFN-alpha (IU/ml) was detectable in 20 (13%) cases. The difference among median PCT values of the bacteraemic (4.22; 1.56-7.56), non-bacteraemic typical bacterial (1.47; 0.24-4.07), atypical bacterial (0.18; 0.06-1.03) and only viral (0.65; 0.11-2.22) subgroups was significant (p = 0.02). PCT was >= 2 ng/ml in 52 (33%) cases. The presence of IFN-alpha was associated with PCT <2 ng/ml (90% vs. 64%, p = 0.02). The negative predictive value (95% confidence interval) of PCT >= 2 ng/ml was 95% (89-100%), 89% (78-100%), 93% (85-100%) for differentiation of bacteraemic from viral, atypical bacterial and non-bacteraemic typical bacterial infection, respectively, and 58% (49-68%) for differentiation between bacterial and viral infection. PCT may be useful in identifying bacteraemia among children hospitalized with community-acquired pneumonia. IFN-alpha was uncommonly detected.

Sole infection by human metapneumovirus among children with radiographically diagnosed community-acquired pneumonia in a tropical region

Background Limited information is available on the role of human metapneumovirus (HMPV) as the unique pathogen among children hospitalized for community-acquired pneumonia (CAP) in a tropical region. Objective We aimed to describe HMPV infection among children with CAP investigating bacterial and viral co-infections. Patients and methods A prospective study was carried out in Salvador, North-East Brazil. Overall, 268 children aged <5 years hospitalized for CAP were enrolled. Human metapneumovirus RNA was detected in nasopharyngeal aspirates (NPA) by reverse transcription polymerase chain reaction. Sixteen other bacterial and viral pathogens were investigated by an expanded panel of laboratory methods. Chest X-ray taken on admission was read by an independent paediatric radiologist unaware of clinical information or the established aetiology. Results Human metapneumovirus RNA was detected in NPAs of 11 (4.1%) children, of which 4 (36%) had sole HMPV infection. The disease was significantly shorter among patients with sole HMPV infection in comparison with patients with mixed infection (4 +/- 1 versus 7 +/- 2 days, P = 0.03). Three of those four patients had alveolar infiltrates. Conclusion Sole HMPV infection was detected in children with CAP in Salvador, North-East Brazil. HMPV may play a role in the childhood CAP burden.

The role of respiratory viral infections among children hospitalized for community-acquired pneumonia in a developing country

We report an investigation for 16 bacteria and viruses among 184 children hospitalized with pneumonia in Salvador, Brazil. Etiology was established in 144 (78%) cases. Viral, bacterial, and mixed infections were found in 110 (60%), 77 (42%), and 52 (28%) patients, respectively. Rhinovirus (21%) and Streptococcus pneumoniae (21%) were the most common pathogens. Our results demonstrate the importance of viral and pneumococcal infections among those patients.

O exame direto do lavado broncoalveolar para o diagnóstico precoce de pneumonia nosocomial : um modelo experimental em ratos

A pneumonia nosocomial é a principal causa de infecção nosocomial em unidades de tratamento intensivo e possui alta morbi/mortalidade. A incidência cumulativa varia, conforme os autores, entre limites amplos desde 8% até 51%, dependendo do tipo de paciente e do uso de instrumentação das vias respiratórias. Nos casos específicos das pneumonias de má resolução e da pneumonia associada à ventilação mecânica, o diagnóstico é problemático devido à ausência de uma padronização definitiva, decorrente não só da grande variabilidade fisiopatológica como também da pouca acurácia dos critérios clínicos, microbiológicos e radiológicos. Estes fatos ensejaram a utilização progressiva de técnicas invasivas sofisticadas para coleta de amostras respiratórias endobrônquicas. Entretanto, a validação dessas técnicas para uso sistemático depende ainda de estudos que avaliem não só o seu custo/benefício em cenários clínicos diversos como também a comparação de seu desempenho para o diagnóstico com um padrão-ouro histopatológico. Além disso, o rendimento das técnicas invasivas é freqüentemente limitado quando são aplicadas em pacientes sob antibioticoterapia, que constituem a maioria dos casos em unidades de cuidados intensivos. A otimização desses testes, discutindo suas indicações e avaliando sua capacidade técnica para a confirmação ou exclusão de pneumonia, é justificada pela necessidade da instituição precoce e correta do tratamento, pois disto resulta menor mortalidade, redução de custos e permanência no hospital. Entre os testes que podem auxiliar no diagnóstico encontra-se o exame direto do lavado broncoalveolar, que proporciona resultados precoces e úteis para a tomada de decisão, mas não suficientemente testados em diferentes situações clínicas ou experimentais. Com o objetivo de avaliar o rendimento diagnóstico do exame direto precoce e das culturas quantitativas obtido por lavado broncoalveolar, estudou-se sua utilização em um modelo experimental de pneumonia provocada através de inoculação bacteriana intrabrônquica em ratos. O estudo comparou a acurácia do exame direto e dos exames culturais em três grupos de animais: Grupo A com pneumonia pneumocócica (37 animais); Grupo P com pneumonia por P. aeruginosa (26 animais) e Grupo B controle (10 animais), utilizando a histopatologia dos pulmões como teste de referência para o diagnóstico. Os Grupos A e P foram ainda randomizados em dois subgrupos cada, para tratamento ou não com antibióticos, usando penicilina no grupo pneumococo e amicacina no grupo Pseudomonas. Como resultado, observou-se que nos animais com pneumonia e ausência de antibióticos a pesquisa de bactéria fagocitada (BIC) no exame direto mostrou um rendimento elevado para o diagnóstico, sendo superior ao das culturas quantitativas. No grupo com pneumonia pneumocócica a BIC mostrou: S:94,4% a 100%, E:100%, VPP:100% e VPN:100%; e as culturas quantitativas mostraram: S:77,8%, E:100%, VPP:100%, VPN:40%. Nos com pneumonia por Pseudomonas a BIC obteve: S: 69%, E:100%; VPP:100% e VPN:71,4%); e as culturas quantitativas mostraram valores muito baixos: S:28,6%, E:100%, VPP:100% e VPN:50%). Nos animais com pneumonia pneumocócica sob tratamento antibiótico havia uma queda acentuada de sensibilidade das culturas quantitativas (S:21%) e, em menor grau da BIC (S:57,9%), mas sem perda da especificidade de ambos os exames. Ao contrário, nos animais com pneumonias por Pseudomonas sob tratamento não havia alteração no rendimento dos dois exames, cujos resultados foram semelhantes aos dos animais sem tratamento. Não havia diferenças de leitura da BIC para o diagnóstico, contando a sua positividade em macrófagos ou em neutrófilos infectados. A avaliação global dos casos estudados, reunindo todos os grupos (tratados e não-tratados) em ambos os modelos de pneumonia, mostrou que a acurácia do exame direto, representado pela pesquisa da BIC, foi superior (66%) ao das culturas quantitativas (53%). As conclusões principais do estudo foram: 1) o exame direto do lavado broncoalveolar (LBA) mostrou-se um teste útil e de alto rendimento para o diagnóstico de pneumonia quando realizado na ausência de antibióticos; 2) o LBA feito na vigência de antibióticos efetivos para a pneumonia perde mais de 50% de sua acurácia, mas não é afetado quando o antibiótico for ineficaz ou houver resistência ao mesmo; 3) a pesquisa de BIC no LBA é um exame de resultado precoce, de alta especificidade e com melhor rendimento do que as culturas quantitativas.

Valor prognóstico das cinéticas da procalcitonina e da proteína C reativa na pneumonia associada à ventilação mecânica

Introdução A pneumonia hospitalar é a principal causa de morte dentre as infecções hospitalares. A prevalência de pneumonia hospitalar em Unidades de Tratamento Intensivo (UTI) varia de 10 a 65%, com taxas de mortalidade que podem variar de 24 a 76%. A pneumonia associada à ventilação mecânica (PAV) é um determinante de mortalidade independente em pacientes submetidos à ventilação mecânica. A adequação do tratamento empírico precoce parece ser fundamental no prognóstico. Os critérios atualmente estabelecidos para avaliar adequação do tratamento empírico utilizam parâmetros clínicos, escores de gravidade e, principalmente, a sensibilidade do germe causador da infecção aos antibióticos administrados. Estes resultados balizam a necessidade de possíveis modificações no esquema antimicrobiano. A possibilidade de utilizar a Procalcitonina (PCT), a Proteína-C Reativa (CRP) e o escore SOFA (Avaliação de Falência de Órgãos Relacionada a Sepse), como indicadores de resposta do paciente, comparando seu status no dia do início do tratamento antimicrobiano (D0) com a evolução destes indicadores no quarto dia de tratamento (D4) abre a possibilidade de comparar o paciente com ele próprio, independente da exuberância da expressão da resposta inflamatória que ele possa desenvolver. Os resultados desta cinética entre D0 e D4 podem ser preditivos de gravidade de infecção, de eficiência antimicrobiana, e possivelmente de sobrevivência ou mortalidade hospitalar nos pacientes com suspeita de PAV. Objetivos Determinar e comparar o valor prognóstico de sobrevivência da cinética da PCT, da CRP, dos escores clínicos CPIS (Escore Clínico de Infecção Pulmonar) e SOFA, e do APACHE II (Avaliação da Fisiologia Aguda e da Saúde Crônica) na PAV entre o diagnóstico e o quarto dia de tratamento, quando a adequação do tratamento é avaliada. Pacientes e Métodos Realizamos um estudo de coorte prospectivo observacional que avaliou 75 pacientes internados no Centro de Tratamento Intensivo clínico-cirúrgico de adultos do Hospital de Clínicas de Porto Alegre que desenvolveram PAV no período de outubro de 2003 a agosto de 2005. Os pacientes com suspeita clínica de PAV que se adequaram aos critérios de inclusão e exclusão do estudo foram os candidatos a participar. Os familiares ou representantes dos pacientes receberam esclarecimentos por escrito acerca dos exames a serem realizados, bem como dos objetivos gerais da pesquisa. Os que aceitaram participar do estudo assinaram o termo de Consentimento Informado. O projeto foi aprovado pelo Comitê de Ética em Pesquisa do Hospital de Clínicas de Porto Alegre. No dia do diagnóstico de PAV foram coletados aspirado traqueal quantitativo, hemoculturas e sangue para a realização de dosagens de PCT, CRP, hemograma, plaquetas, creatinina, bilirrubinas, gasometria arterial e radiografia de tórax, com o objetivo de calcular o CPIS e o escore SOFA. No terceiro dia de tratamento foram novamente coletados aspirados traqueais quantitativos e os demais exames para o cálculo do CPIS. No quarto dia foi coletado sangue para dosagens de PCT, CRP e para os demais exames necessários para o cálculo do SOFA. Os pacientes foram acompanhados por 28 dias após o diagnóstico de PAV, quando foram considerados sobreviventes. Todos os pacientes que morreram antes do vigésimo oitavo dia foram considerados não-sobreviventes. Resultados Os níveis de PCT foram mais baixos nos sobreviventes em D0 (p=0.003) e em D4 (p=0.001). Os níveis de CRP não foram diferentes em sobreviventes e nãosobreviventes em D0 (p=0.77) e em D4 (p=0.14). O CPIS não pode diferenciar sobreviventes de não-sobrevientes em D0 (p=0.32) e em D3 (p=0.45). ΔCPIS decrescente não foi correlacionado a sobrevivência (p=0.59), o mesmo ocorrendo com CPIS <6 em D3 (p=0.79). Pacientes que morreram antes de D4 não puderam ter sua cinética calculada e foram considerados casos perdidos. Variáveis incluídas no modelo de regressão logística univariável para sobrevivência foram idade, APACHE II, ΔSOFA decrescente, ΔPCT decrescente e ΔCRP decrescente. Sobrevivência foi diretamente correlacionada a ΔPCT decrescente com RC = 5.67 (1.78;18.03) p = 0.003, ΔCRP com RC = 3.78 (1.24;11.50) p = 0.02, ΔSOFA decrescente com RC = 3.08 (1.02;9.26) p = 0.05 e escore APACHE II com RC = 0.92 (0.86;0.99) p = 0.02. O modelo de regressão logística multivariável para sobrevivência incluiu todas as variáveis participantes da análise univariável. Somente ΔPCT decrescente com RC = 4.43 (1.08;18.18) p = 0.04 e ΔCRP com RC = 7.40 (1.58;34.73) p = 0.01 permaneceram significativos. A avaliação da cinética dos marcadores inflamatórios e a associação com sobrevida no estudo mostraram que: - Em 95,1% dos sobreviventes houve queda dos níveis de PCT ou de CRP. - Em 61% dos sobreviventes ambos os níveis de PCT e de CRP caíram. Apenas 4,9% dos sobreviventes tiveram níveis de PCT e CRP crescentes. Com relação aos não-sobreviventes, 78.9% tiveram pelo menos um dos dois marcadores ou ambos com níveis crescentes. Conclusão As cinéticas da PCT e da CRP, obtidas pelas dosagens de seus níveis no dia do diagnóstico e no 4º dia de tratamento, podem predizer sobrevivência em pacientes com PAV. A queda dos níveis de pelo menos um destes marcadores ou de ambos indica maior chance de sobrevivência.

Antibiotic treatment schemes for very severe community-acquired pneumonia in children: a randomized clinical study

Objective. To compare clinical response to initial empiric treatment with oxacillin plus ceftriaxone and amoxicillin plus clavulanic acid in hospitalized children diagnosed with very severe community-acquired pneumonia (CAP).Methods. A prospective randomized clinical study was conducted among children 2 months to 5 years old with a diagnosis of very severe CAP in the pediatric ward of São Paulo State University Hospital in Botucatu, São Paulo, Brazil, from April 2007 to May 2008. Patients were randomly divided into two groups by type of treatment: an oxacillin/ceftriaxone group (OCG, n = 48) and an amoxicillin/clavulanic acid group (ACG, n = 56). Analyzed outcomes were: time to clinical improvement (fever and tachypnea), time on oxygen therapy, length of stay in hospital, need to widen antimicrobial spectrum, and complications (including pleural effusion).Results. The two groups did not differ statistically for age, sex, symptom duration before admission, or previous antibiotic treatment. Time to improve tachypnea was less among ACG patients than OCG patients (4.8 +/- 2.2 versus 5.8 +/- 2.4 days respectively; P = 0.028), as was length of hospital stay (11.0 +/- 6.2 versus 14.4 +/- 4.5 days respectively; P = 0.002). There were no statistically significant differences between the two groups for fever improvement time, time on oxygen therapy, need to widen antimicrobial spectrum, or frequency of pleural effusion.Conclusions. Both treatment plans are effective in treating very severe CAP in 2-monthto 5-year-old hospitalized children. The only analyzed outcome that favored amoxicillin/clavulanic acid treatment was time required to improve tachypnea.

Pesquisa epidemiológica e molecular do vírus respiratório sincicial humano (VSRH) em amostras de pacientes hospitalizados com pneumonia, na cidade de Belém

A pneumonia e a bronquiolite na infância são as principais causas de morbidade e mortalidade no mundo, sendo o Vírus Respiratório Sincicial Humano (VSRH) o principal agente viral. O VSRH está associado a surtos anuais de doenças respiratórias, onde a co-infecção bacteriana tem sido relatada. Este foi o primeiro estudo do VRSH em crianças hospitalizadas com Pneumonia Adquirida na Comunidade (PAC) em Belém, Pará (Norte do Brasil), que teve como objetivo determinar a prevalência da infecção pelo VSRH e avaliar as características clínicas e epidemiológicas dos pacientes. Métodos. Foi realizado um estudo prospectivo em oito hospitais no período de novembro de 2006 a outubro de 2007. Foram testadas 1.050 amostras de aspirado nasofaríngeo para o VRSH, obtidas de crianças hospitalizadas com até três anos de idade com diagnóstico de PAC, pelo método da imunofluorescência direta e da reação em cadeia por polimerase após transcrição reversa (RT-PCR) para identificação do subtipo viral. Foram obtidos resultados da dosagem de proteína C-reativa (PCR) e da cultura bacteriana. Resultados. A infecção pelo VSRH foi diagnosticada em 243 (23,1%) crianças. A idade média do grupo VRSH-positivo foi menor do que a do grupo VRSH-negativo (12,1 meses versus (vs) 15,5 meses, ambos com variância de 1-36 meses, p<0,001), enquanto que a distribuição por genero foi similar. O grupo VRSH-positivo apresentou menor dosagem (PCR) quando comparados ao grupo VRSH-negativo (15,3 vs 24.0 mg/dL, p<0,05). Os achados radiológicos confirmaram que 54,2% do grupo VRSH-positivo e 50,3% do grupo VRSH-negativo apresentavam infiltrado intersticial. A infecção bacteriana foi identificada predominantemente no grupo VRSH-positivo (10% vs 4,5%, p<0,05). Rinorréia e obstrução nasal foram predominantemente observadas no grupo VRSH-positivo. A co-circulação dos subtipos A e B foi observada, com predominância do subtipo B (209/227). A análise multivariada revelou que a idade de 1 ano (p<0,015), os níveis de PCR inferior a 48 mg/dL (p<0,001) e a co-infecção bacteriana (p<0,032) foram independentemente associados com a presença do VRSH em oposição ao grupo VRSH-negativo, e na análise dos sintomas, a obstrução nasal foi independentemente associada com o grupo VRSH-positivo (p<0,001). Conclusão. O presente estudo destaca a relevância da infecção por VSRH em casos hospitalizados de PAC em nossa região; nossos resultados justificam a realização de investigações adicionais que possam ajudar a elaborar estratégias para o controle da doença.

Association between systemic corticosteroids and outcomes of intensive care unit-acquired pneumonia

Objective: The use of corticosteroids is frequent in critically-ill patients. However, little information is available on their effects in patients with intensive care unit acquired pneumonia. We assessed patients' characteristics, microbial etiology, inflammatory response, and outcomes of previous corticosteroid use in patients with intensive care unit acquired pneumonia. Design: Prospective observational study. Setting: Intensive care units of a university teaching hospital. Patients: Three hundred sixteen patients with intensive care unit acquired pneumonia. Patients were divided according to previous systemic steroid use at onset of pneumonia. Interventions: None. Measurements and Main Results: Survival at 28 days was analyzed using Cox regression, with adjustment for the propensity for receiving steroid therapy. One hundred twenty-five (40%) patients were receiving steroids at onset of pneumonia. Despite similar baseline clinical severity, steroid treatment was associated with decreased 28-day survival (adjusted hazard ratio for propensity score and mortality predictors 2.503; 95% confidence interval 1.176-5.330; p = .017) and decreased systemic inflammatory response. In post hoc analyses, steroid treatment had an impact on survival in patients with nonventilator intensive care unit acquired pneumonia, those with lower baseline severity and organ dysfunction, and those without etiologic diagnosis or bacteremia. The cumulative dosage of corticosteroids had no significant effect on the risk of death, but bacterial burden upon diagnosis was higher in patients receiving steroid therapy. Conclusions: In critically-ill patients, systemic corticosteroids should be used very cautiously because this treatment is strongly associated with increased risk of death in patients with intensive care unit acquired pneumonia, particularly in the absence of established indications and in patients with lower baseline severity. Decreased inflammatory response may result in delayed clinical suspicion of intensive care unit acquired pneumonia and higher bacterial count. (Crit Care Med 2012; 40:2552-2561)

Community-acquired pneumonia in Chile: the clinical relevance in the detection of viruses and atypical bacteria

Background Adult community-acquired pneumonia (CAP) is a relevant worldwide cause of morbidity and mortality, however the aetiology often remains uncertain and the therapy is empirical. We applied conventional and molecular diagnostics to identify viruses and atypical bacteria associated with CAP in Chile. Methods We used sputum and blood cultures, IgG/IgM serology and molecular diagnostic techniques (PCR, reverse transcriptase PCR) for detection of classical and atypical bacteria (Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumoniae) and respiratory viruses (adenovirus, respiratory syncytial virus (RSV), human metapneumovirus, influenza virus, parainfluenzavirus, rhinovirus, coronavirus) in adults >18 years old presenting with CAP in Santiago from February 2005 to September 2007. Severity was qualified at admission by Fine's pneumonia severity index. Results Overall detection in 356 enrolled adults were 92 (26%) cases of a single bacterial pathogen, 80 (22%) cases of a single viral pathogen, 60 (17%) cases with mixed bacterial and viral infection and 124 (35%) cases with no identified pathogen. Streptococcus pneumoniae and RSV were the most common bacterial and viral pathogens identified. Infectious agent detection by PCR provided greater sensitivity than conventional techniques. To our surprise, no relationship was observed between clinical severity and sole or coinfections. Conclusions The use of molecular diagnostics expanded the detection of viruses and atypical bacteria in adults with CAP, as unique or coinfections. Clinical severity and outcome were independent of the aetiological agents detected.

Surveillance of antimicrobial resistance of Streptococcus pneumoniae and Haemophilus influenzae in children with pneumonia

In order to identify optimal therapy for children with bacterial pneumonia, Pakistan's ARI Program, in collaboration with the National Institute of Health (NIH), Islamabad, undertook a national surveillance of antimicrobial resistance in S. pneumoniae and H. influenzae. The project was carried out at selected urban and peripheral sites in 6 different regions of Pakistan, in 1991–92. Nasopharyngeal (NP) specimens and blood cultures were obtained from children with pneumonia diagnosed in the outpatient clinic of participating facilities. Organisms were isolated by local hospital laboratories and sent to NIH for confirmation, serotyping and antimicrobial susceptibility testing. Following were the aims of the study (i) to determine the antimicrobial resistance patterns of S. pneumoniae and H. influenzae in children aged 2–59 months; (ii) to determine the ability of selected laboratories to identify and effectively transport isolates of S. pneumoniae and H. influenzae cultured from nasopharyngeal and blood specimens; (iii) to validate the comparability of resistance patterns for nasopharyngeal and blood isolates of S. pneumoniae and H. influenzae from children with pneumonia; and (iv) to examine the effect of drug resistance and laboratory error on the cost of effectively treating children with ARI. ^ A total of 1293 children with ARI were included in the study: 969 (75%) from urban areas and 324 (25%) from rural parts of the country. Of 1293, there were 786 (61%) male and 507 (39%) female children. The resistance rate of S. pneumoniae to various antibiotics among the urban children with ARI was: TMP/SMX (62%); chloramphenicol (23%); penicillin (5%); tetracycline (16%); and ampicillin/amoxicillin (0%). The rates of resistance of H. influenzae were higher than S. pneumoniae: TMP/SMX (85%); chloramphenicol (62%); penicillin (59%); ampicillin/amoxicillin (46%); and tetracycline (100%). There were similar rates of resistance to each antimicrobial agent among isolates from the rural children. ^ Of a total 614 specimens that were tested for antimicrobial susceptibility, 432 (70.4%) were resistant to TMP/SMX and 93 (15.2%) were resistant to antimicrobial agents other than TMP/SMX viz. ampicillin/amoxicillin, chloramphenicol, penicillin, and tetracycline. ^ The sensitivity and positive predictive value of peripheral laboratories for H. influenzae were 99% and 65%, respectively. Similarly, the sensitivity and positive predictive value of peripheral laboratory tests compared to gold standard i.e. NIH laboratory, for S. pneumoniae were 99% and 54%, respectively. ^ The sensitivity and positive predictive value of nasopharyngeal specimens compared to blood cultures (gold standard), isolated by the peripheral laboratories, for H. influenzae were 88% and 11%, and for S. pneumoniae 92% and 39%, respectively. (Abstract shortened by UMI.)^

Streptococcus pneumoniae detects and responds to foreign bacterial peptide fragments in its environment

Streptococcus pneumoniae is an important cause of bacterial meningitis and pneumonia but usually colonizes the human nasopharynx harmlessly. As this niche is simultaneously populated by other bacterial species, we looked for a role and pathway of communication between pneumococci and other species. This paper shows that two proteins of non-encapsulated S. pneumoniae, AliB-like ORF 1 and ORF 2, bind specifically to peptides matching other species resulting in changes in the pneumococci. AliB-like ORF 1 binds specifically peptide SETTFGRDFN, matching 50S ribosomal subunit protein L4 of Enterobacteriaceae, and facilitates upregulation of competence for genetic transformation. AliB-like ORF 2 binds specifically peptides containing sequence FPPQS, matching proteins of Prevotella species common in healthy human nasopharyngeal microbiota. We found that AliB-like ORF 2 mediates the early phase of nasopharyngeal colonization in vivo. The ability of S. pneumoniae to bind and respond to peptides of other bacterial species occupying the same host niche may play a key role in adaptation to its environment and in interspecies communication. These findings reveal a completely new concept of pneumococcal interspecies communication which may have implications for communication between other bacterial species and for future interventional therapeutics.