In this thesis I will review the current knowledge of community-acquired pneumonia, including its classification, pathogenesis, pathology, aetiology, diagnosis, and antibiotic therapy and report my experience with severe community-acquired pneumonia in patients requiring admission to our respiratory intensive care unit. The original research in this thesis comprises a prospective, descriptive analysis of 196 cases of severe community-acquired pneumonia requiring admission to the Respiratory Intensive Unit at Groote Schuur Hospital from January 1987 until December 1992, with emphasis on the influence of aetiology on the severity of pneumonia, the· aetiological diagnosis of pneumonia in severely ill patients, measures of severity of pneumonia, and an audit of ICU therapy and outcome. In addition, different aspects of novel therapies and specific aetiological varieties of pneumonia which have been investigated over the past ten years will be presented.

No description available.

Thesis (M.Med. (Internal Medicine))--University of the Witwatersrand, Faculty of Health Sciences, 2013. / Background Cryptococcus is a life-threatening opportunistic infection; data is limited regarding early infection. Treatment of cryptococcal antigenaemia may impact on disease progression. Screening those most at risk for cryptococcal antigenaemia is necessary to be cost effective. The prevalence of cryptococcal antigenaemia in patients hospitalised with community acquired pneumonia (CAP) at Chris Hani Baragwanath Academic Hospital (CHBAH) was evaluated. Methods 200 patients admitted to CHBAH with presumed CAP were enrolled. Clinical and laboratory data were collected and a Cryptococcal Lateral Flow Immunoassay was done on whole blood. Results Of the 200 patients, 185 (92.5%) were HIV-infected. Amongst the HIV-infected group, the median CD4 cell count was 47 cells/mm3 and 111 subjects (60%) had a CD4 cell count < 100 cells/mm3. The prevalence of cryptococcal antigenaemia was 0.5% (CI 0.01-2.75). Conclusion The prevalence of cryptococcal antigenaemia amongst inpatients with CAP was low. Routine screening of this group would not be cost-effective.

Methicillin-resistant Staphylococcus aureus (MRSA) is a successful pathogen which was historically found in hospital settings but now is a common cause of infection in communities. The rapid emergence of community-acquired MRSA (CA-MRSA) at the turn of the 21st century has established this bacterium’s presence throughout the globe and MRSA continues to be endemic in certain countries. Asia is the most populous continent in the world and also holds a high burden of MRSA infection. This presents a concern for both public health and the acquisition of antibiotic resistance in this region. This literature review describes how MRSA became a successful pathogen. It provides a systematic review of the recent literature on MRSA in East Asia to identify major MRSA clones by country as determined by their molecular characteristics. Also to identify notable genetic and epidemiological factors associated with these MRSA clones. The results of this survey provided evidence of the importance of using molecular categorization techniques to accurately distinguish MRSA strains that require specific antibiotic treatment methods. It also provided evidence of CA-MRSA clones invading hospital settings and traditional hospital-acquired MRSA (HA-MRSA) clones continuing to develop multi-drug resistance throughout East Asian countries. The results also detected novel MRSA strains across hospitals and reported the spread of major MRSA clones within and between countries. Strengthening existing surveillance systems and collaborative efforts between countries within Asia should be a priority to monitor the evolution and movement MRSA especially in the age of globalization and accessible travel.

Abstract Systematic analyses of infections in critical illness are sparse and mostly restricted to specific infection categories. Thus, a prospective study was carried out in a medical-surgical ICU during 14 months on patients whose ICU stay was longer than 48 h. The prospectively gathered data included detailed patient history, infection survey, severity of illness scores (APACHE II, SOFA), resource use, short-term and long-term outcome and quality of life following hospital discharge. Altogether 335 patients were included, of whom 251 (74.9%) had an infection on admission; 59.3% had a community-acquired infection (CAI) and 40.7% a hospital-acquired infection (HAI), while 84 (25.1%) did not have any infection (NI). APACHE II scores and ICU or hospital mortality rates did not differ between the groups. The median hospital stay was longer in the HAI than in the CAI or NI groups. Eighty (23.9%) of the 335 patients developed an ICU-acquired infection (48 per 1000 patient days): ventilator-associated pneumonia (VAP) in 33.8% of the cases, central catheter-related (CRI) or primary bloodstream infections in 6.3% and urinary tract infections in 1.3%, while the corresponding device-related incidences per 1000 days were 18.8, 2.2 and 0.5, respectively. ICU-acquired infection was an independent risk factor for hospital mortality. It doubled the risk for hospital mortality in patients with an infection on admission and caused a threefold the risk in patients without an infection on admission and an almost fourfold increase in the use of nursing resources. Of the 272 hospital survivors, 83 (30.5%) died after discharge during the median follow-up of 17 weeks. Infection status on admission or during the ICU stay did not affect long-term mortality. ICU-acquired infection did not have an impact on patients' quality of life. The current general level of health compared to the status before ICU admission did not differ between the groups, either. Only 36% of those employed resumed their previous jobs. Three-fourths of patients had an infection on admission, while nearly one fourth acquired an ICU infection. The high VAP rate suggests a need for re-evaluation of preventive measures, whereas the low CRI indicates more successful prevention. ICU-acquired infection was a significant risk factor for hospital mortality, but did not affect patients' long-term survival or quality of life.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 5 uppsatser.

Background: Community acquired pneumonia causes 5,9% of deaths in elderly South Africans. Mortality rates are increased in those in whom initiation of therapy with an appropriate agent has been delayed. Whereas Mycoplasma pneumoniae and Legionella pneumophila are sensitive to the macrolides or tetracycline, they do not respond to the currently recommended first-line agents for community acquired pneumonia, penicillin or a cephalosporin. It was therefore necessary to assess the prevalence of exposure to these 2 organisms in the elderly in order to determine whether a modification in the recommendations may be justified. Methods: Study population and survey: Subjects were residents of 4 old age homes in Cape Town who were older than 60 years and willing to participate. Written consent was obtained, a demographic and medical history questionnaire was completed, and a sample of blood was drawn. Laboratory methods: The indirect fluorescent antibody tests (Zeus Scientific Inc, New Jersey, USA) were used to detect the presence of antibodies to Mycoplasma pneumoniae and Legionella pneumophila. Results: The participation rate in this study was high, with 88,4% (677/766) taking part. Seropositivity for both of these organisms was low. There were 17 participants (2, 51 %) with antibodies to mycoplasma (IgG only in 8, IgM only in 1, and both IgG and IgM in the remaining 8). Titres were low with only 1 IgM titre of 16, and only 3 IgG titres of 64. Antibodies to Legionella were demonstrated in only 9 participants (1,33%). All these titres were 128 or above. Conclusions: It is concluded that first-line therapy for community acquired pneumonia should adhere to the current guidelines published by the South African Pulmonology Society. There is no indication for the routine use of agents active against Legionella or mycoplasma. Clearly, these antibiotics should be introduced if specific pointers to infection with one of these organisms are found. Because of the low seropositivity rate, the indirect fluorescent antibody test for these 2 agents has a high specificity in this population. This may be of use in making a diagnosis in an acute infection Further studies are required to elucidate the immunological response to these organisms in elderly persons. A further survey should be done to determine the seropositivity rate to these agents in community dwelling elderly.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2005. / Härtill 5 uppsatser.

Abstract Pneumonia is a common diagnosis for intensive care unit (ICU) admission. In 2012, 51% of the ICU-treated infections in Finland were of pulmonary origin. The ICU-treated pneumonias can be classified according to acquisition of infection as community-acquired (CAP) or hospital-acquired (HAP). Ventilator-associated pneumonia (VAP) is a subtype of HAP. Patients with severe community-acquired pneumonia (SCAP) require ICU treatment due to need of mechanical ventilation or hemodynamic support. SCAP is associated with high morbidity and high ICU and hospital mortality. The aim of this observational study was to evaluate the clinical characteristics and outcome of SCAP, with special interest on imaging, viral etiology, combination antibiotic treatment and long-term outcome. The thesis comprises three retrospective studies with altogether 392 SCAP patients, median age 55 years, 55.9% of them male. The usefulness of early chest CT and β-lactam-respiratory quinolone (βQ) versus β-lactam-macrolide (βM) therapy for SCAP treatment was evaluated. The hospital and long-term outcomes of SCAP patients were compared with 66 HAP and 25 VAP cases. A prospective study included 49 mechanically ventilated SCAP patients. The frequency of viral etiology in SCAP was analyzed. In SCAP patients, the chest CT as compared to the chest radiograph yielded new imaging findings for 58.5% of the SCAP patients. This information led to procedures or treatment changes in 43% of the cases. The severity of oxygenation disorder correlated to the extent of lung involvement. In prospective SCAP series ICU- mortality was 6.1% and hospital mortality was 12.2%. Viral etiology was found to be common in SCAP and viruses were demonstrated in 49% of patients. The outcome was similar whether SCAP patients were treated with βQ or βM combination. The type of pneumonia did not have a significant association with hospital mortality in ICU-treated SCAP, HAP and VAP patients. Among the hospital survivors, the long-term mortality was substantial, SCAP patients representing the best 1-year outcome. In conclusion, early CT might be useful in SCAP diagnostics and treatment. Viral etiology is common in SCAP. Both β-lactam-respiratory quinolone and β-lactam macrolide combinations were equally good in SCAP treatment. Hospital mortality did not differ among ICU-treated pneumonia cases, but SCAP had the best long-term survival. / Tiivistelmä Keuhkokuume on yleinen tehohoitoon johtava tulehdussairaus. Suomessa vuonna 2012 teho-osastolla hoidetuista infektioista 51&#160;% oli keuhkoalkuisia. Keuhkokuume luokitellaan hankintapaikan mukaan kotisyntyiseksi (CAP) tai sairaalasyntyiseksi (HAP). Hengityslaitehoitoon liittyvä keuhkokuume (VAP) on sairaalasyntyisen keuhkokuumeen alatyyppi. Vakavalla kotisyntyisellä keuhkokuumeella (SCAP) tarkoitetaan vaikeaa keuhkoinfektiota, joka vaatii hengityslaitehoitoa tai verenkierron tukihoitoa teho-osastolla. SCAP:iin liittyy korkea sairastuvuus sekä tehohoito- ja sairaalakuolleisuus. Tässä havainnoivassa kliinisessä tutkimuksessa selvitettiin SCAP:n kliinistä kuvaa ja ennustetta. Erityishuomion kohteena oli varhaisvaiheessa suoritetun keuhkojen tietokonekerroskuvauksen (CT), keuhkokuumeen aiheuttajamikrobien ja antibimikrobihoidon vaikutus taudin hoitoon ja ennusteeseen sekä tehohoidettujen keuhkokuumepotilaiden pitkäaikaisennuste. Väitöskirja koostuu kolmesta retrospektiivisestä osatyöstä, joissa oli yhteensä 392 SCAP-potilasta. Potilaiden mediaani-ikä oli 55 vuotta ja heistä 55,9&#160;% oli miehiä. Varhaisvaiheen keuhkojen CT:n sekä beetalaktaami-kinoloni- ja beetalaktaami- makrolidi-yhdistelmähoidon vaikutusta keuhkokuumeen hoitoon arvioitiin retrospektiivisesti. SCAP-potilaiden sairaalakuolleisuutta ja pitkäaikaisennustetta verrattiin 25:n VAP- ja 66:n HAP-potilaan ennusteeseen. Prospektiivisessa tutkimuksessa oli 49 hengityskonehoidettua potilasta. Tutkimuksessa tarkasteltiin virusten osuutta ja merkitystä vaikeassa SCAP:ssa. Keuhkojen CT havaitsi 58,5&#160;%:lla SCAP-potilaista löydöksiä, joita ei todettu keuhkojen natiiviröntgentutkimuksessa. Löydökset johtivat toimenpiteisiin 43&#160;%:lla SCAP-potilaista. Happeutumishäiriön vaikeusasteen ja CT:llä todettujen keuhkojen tulehdusmuutosten laajuuden välillä havaittiin yhteys. Virusetiologia on SCAP:ssa yleinen. Viruksia havaittiin 49&#160;%:lla SCAP-potilaista. Beetalaktaami-kinoloni- ja beetalaktaami-makrolidi -yhdistelmähoidon välillä ei havaittu eroa SCAP-potilaiden ennusteessa. SCAP-, HAP- ja VAP-potilaiden ennustevertailussa keuhkokuumetyypin ei todettu vaikuttavan sairaalakuolleisuuteen. Paras yhden vuoden ennuste oli SCAP-potilailla. Yhteenvetona todettakoon, että varhaisvaiheen keuhkojen CT on hyödyllinen SCAP:n hoidossa. Virukset ovat yleisiä SCAP:n aiheuttajamikrobeja. Molemmat tutkitut antimikrobiyhdistelmät todettiin hyviksi SCAP:n hoidossa. Sairaalakuolleisuus ei eroa keuhkokuumealatyyppien välillä, mutta SCAP- potilailla on paras pitkäaikaisennuste.

O objetivo principal dessa tese foi avaliar se o tratamento com ceftriaxona e um macrolídeo leva a melhores desfechos quando comparada a monoterapia com ceftriaxona em pacientes hospitalizados com HIV/AIDS e pneumonia adquirida na comunidade (PAC). 227 adultos com HIV hospitalizados por uma suspeita de PAC foram randomizados numa proporção 1:1 para receber um dos dois regimes, ceftriaxona mais macrolídeo ou ceftriaxona mais placebo. Houve 2 exclusões após a randomização, um paciente retirou consentimento para uso de seus dados e outro paciente já havia sido incluído previamente no estudo, perfazendo um total de 225 pacientes analisados (112 receberam ceftriaxona mais placebo e 113 receberam ceftriaxona mais macrolídeo). Os pacientes tinham HIV há um longo tempo (período mediano de 10 anos) e a maioria não fazia uso regular de terapia antirretroviral. Somente 32/202 pacientes (16%) tinham carga viral menor que 50 cópias/mL e 146/202 (72%) tinham contagem de linfócitos T CD4+ menor que 200 células/mm³. A frequência do desfecho primário, letalidade durante a internação, não foi estatisticamente distinta entre os regimes estudados: 12/112 (11%) pacientes que receberam ceftriaxona mais placebo e 17/113 (15%) que receberam ceftriaxona mais macrolídeo foram a óbito durante a hospitalização (HR: 1.22, 95% CI: 0.57-2.59). Não foram encontradas diferenças entre os regimes para os desfechos secundários: letalidade em 14 dias (RR: 2.38, 95% CI: 0.87-6.53), uso de drogas vasoativas (OR: 1.18, 95% CI: 0.60-2.29) e ventilação mecânica (OR: 1.24, 95% CI: 0.64- 2.40). A etiologia das infecções pulmonares adquiridas na comunidade nesses pacientes com infecção pelo HIV também foi estudada e determinada prospectivamente. Essa investigação também buscou analisar a contribuição de diferentes métodos diagnósticos e o impacto de diferentes abordagens de investigação microbiológica. Além disso, os achados microbiológicos foram analisados levando em consideração a contagem de linfócitos T CD4+, gravidade da doença e a situação da vacina pneumocócica. 224 pacientes foram submetidos a investigação microbiológica estendida e 143 (64%) tiveram uma etiologia determinada. Por outro lado, a investigação microbiológica de rotina foi capaz de determinar o agente etiológico em 92 (41%) pacientes. Métodos baseados na reação em cadeia da polimerase foram essenciais para o diagnóstico de bactérias atípicas e vírus, além de melhorar a detecção de Pneumocystis jirovecii. Entre os 143 pacientes com uma etiologia determinada, Pneumocystis jirovecii foi o principal agente, detectado em 52 (36%) casos, seguido pelo Mycobacterium tuberculosis responsável por 28 (20%) casos. Streptococcus pneumoniae e Rhinovírus foram diagnosticados em 22 (15%) casos cada e Influenza em 15 (10%) casos. Entre as bactérias atípicas, Mycoplasma pneumoniae foi responsável por 12 (8%) e Chlamydophila pneumoniae por 7 (5%) casos. Infecções mistas ocorreram em 48 casos (34%). Streptococcus pneumoniae foi associado com maiores escores de gravidade, sem associação com o estado vacinal. A análise de agentes etiológicos baseada na contagem de linfócitos T CD4+ demonstrou que a etiologia da pneumonia nos pacientes que estavam gravemente imunossuprimidos (CD4+ < 200 células/mm³) foi similar aos que não estavam. Pneumocystis jirovecii foi o único agente mais frequente no primeiro grupo, um achado esperado levando em consideração os critérios diagnósticos empregados / The main purpose of this thesis was to evaluate if treatment with ceftriaxone and a macrolide improved patient outcome when compared with monotherapy with ceftriaxone in hospitalized patients with HIV/AIDS with community acquired pneumonia (CAP). 227 adult patients with HIV hospitalized due to suspected CAP were randomized to receive one of two regimens, ceftriaxone plus macrolide or ceftriaxone plus placebo, at a 1:1 proportion. We had 2 exclusions after randomization, one patient who withdrew consent for data inclusion and use and one that had previously been included, leaving a total of 225 patients to analyse (112 received ceftriaxone plus placebo and 113 received ceftriaxone plus macrolide). Patients had prolonged HIV infection, the median period was twelve years, and most of them did not make regular use of antiretroviral therapy. Only 32/202 patients (16%) had viral load below 50 copies/mL and 146/202 (72%) had a CD4+ T cell count below 200 cells/mm³. The frequency of the primary outcome, in-hospital mortality, was not statistically different between the studied regimens: 12/112 (11%) patients who received ceftriaxone plus placebo and 17/113 (15%) who received ceftriaxone plus macrolide died during hospitalization (HR: 1.22, 95% CI: 0.57-2.59). We did not find differences between the regimens for the secondary outcomes: mortality within 14 days (RR: 2.38, 95% CI: 0.87-6.53), need for vasoactive drug (OR: 1.18, 95% CI: 0.60-2.29) or mechanical ventilation (OR: 1.24, 95% CI: 0.64-2.40). The etiology of community-acquired pulmonary infections in these hospitalized patients with HIV was also studied and determined prospectively. This investigation also aimed to analyze the contribution of different diagnostic methods as well of the impact of different approaches to microbiological evaluation and to evaluate the microbiological findings in relation to the CD4+ T cell count, the severity of disease and pneumococcal vaccine status. 224 patients underwent the extended microbiological investigation of which 143 (64%) had an etiology determined. On the other hand, the microbiological routine investigation was able to determine the etiological agents in 92 (41%) patients. Polymerase chain reaction-based methods were essential for the diagnosis of atypical bacteria and viruses, besides contributing to ameliorate Pneumocystis jirovecii detection. Among the 143 patients with a determined etiology, Pneumocystis jirovecii was the main agent, detected in 52 (36%) cases and followed by Mycobacterium tuberculosis accounting for 28 (20%) cases. Streptococcus pneumoniae and Rhinovirus were diagnosed in 22 (15%) cases each and Influenza in 15 (10%) cases. Among atypical bacteria, Mycoplasma pneumoniae was responsible for 12 (8%) and Chlamydophila pneumoniae for 7 (5%) cases. Mixed infections occurred in 48 cases (34%). Streptococcus pneumoniae was associated with higher severity scores and not associated with vaccine status. Performing an analysis of causative agents based on CD4+ T cell count, we found that the etiology of pneumonia in those severely immunosuppressed (CD4+ < 200 cells/mm³) was similar to those who were not. Pneumocystis jirovecii is the only agent more frequent in the former group, an expected finding considering our diagnostic criteria