Pro-adrenomedullin usefulness in the management of children with community-acquired pneumonia, a preliminary prospective observational study

BackgroundIn adult population with community acquired pneumonia high levels of pro-adrenomedullin (pro-ADM) have been shown to be predictors of worse prognosis. The role of this biomarker in pediatric patients had not been analyzed to date. The objective of this study is to know the levels of pro-ADM in children with community acquired pneumonia (CAP) and analyze the relation between these levels and the patients¿ prognosis.FindingsProspective observational study including patients attended in the emergency service (January to October 2009) admitted to hospital with CAP and no complications at admission. The values for pro-ADM were analyzed in relation to: need for oxygen therapy, duration of oxygen therapy, fever and antibiotic therapy, complications, admission to the intensive care unit, and length of hospital stay. Fifty patients were included. Ten presented complications (7 pleural effusion). The median level of pro-ADM was 1.0065¿nmol/L (range 0.3715 to 7.2840¿nmol/L). The patients presenting complications had higher levels of pro-ADM (2.3190 vs. 1.1758¿nmol/L, p¿=¿0.013). Specifically, the presence of pleural effusion was associated with higher levels of pro-ADM (2.9440 vs. 1.1373¿nmol/L, p¿<¿0.001).ConclusionsIn our sample of patients admitted to hospital with CAP, pro-ADM levels are related to the development of complications during hospitalization.

Etiology of community-acquired pneumonia in hospitalized children based on WHO clinical guidelines.

Community-acquired pneumonia (CAP) is a major cause of death in developing countries and of morbidity in developed countries. The objective of the study was to define the causative agents among children hospitalized for CAP defined by WHO guidelines and to correlate etiology with clinical severity and surrogate markers. Investigations included an extensive etiological workup. A potential causative agent was detected in 86% of the 99 enrolled patients, with evidence of bacterial (53%), viral (67%), and mixed (33%) infections. Streptococcus pneumoniae was accounted for in 46% of CAP. Dehydration was the only clinical sign associated with bacterial pneumonia. CRP and PCT were significantly higher in bacterial infections. Increasing the number of diagnostic tests identifies potential causes of CAP in up to 86% of children, indicating a high prevalence of viruses and frequent co-infections. The high proportion of pneumococcal infections re-emphasizes the importance of pneumococcal immunization.

Listeria brain abscess, Pneumocystis pneumonia and Kaposi's sarcoma after temozolomide.

BACKGROUND: A 55-year-old man with glioblastoma multiforme was treated with continuous, dose-dense temozolomide. This therapy was curtailed after three cycles because of nausea, asthenia, and neuropsychological deterioration. During a subsequent course of radiotherapy, the patient developed fever, headaches, and cutaneous lesions. INVESTIGATIONS: Physical examination, cerebral MRI, brain biopsy, skin biopsy, immunohistochemistry, bronchoscopy with bronchoalveolar lavage, and laboratory tests. DIAGNOSIS: Severe temozolomide-induced immunosuppression, exacerbated by corticosteroids, with profound T-cell lymphocytopenia and simultaneous opportunistic infections with Pneumocystis jiroveci pneumonia, brain abscess with Listeria monocytogenes, and cutaneous Kaposi's sarcoma. MANAGEMENT: Discontinuation of temozolomide, discontinuation of radiotherapy, antibiotic treatment with amoxicillin and gentamicin, and administration of atovaquone and pentamidine.

Clinical predictors for Legionella in patients presenting with community-acquired pneumonia to the emergency department.

BACKGROUND: Legionella species cause severe forms of pneumonia with high mortality and complication rates. Accurate clinical predictors to assess the likelihood of Legionella community-acquired pneumonia (CAP) in patients presenting to the emergency department are lacking. METHODS: We retrospectively compared clinical and laboratory data of 82 consecutive patients with Legionella CAP with 368 consecutive patients with non-Legionella CAP included in two studies at the same institution. RESULTS: In multivariate logistic regression analysis we identified six parameters, namely high body temperature (OR 1.67, p < 0.0001), absence of sputum production (OR 3.67, p < 0.0001), low serum sodium concentrations (OR 0.89, p = 0.011), high levels of lactate dehydrogenase (OR 1.003, p = 0.007) and C-reactive protein (OR 1.006, p < 0.0001) and low platelet counts (OR 0.991, p < 0.0001), as independent predictors of Legionella CAP. Using optimal cut off values of these six parameters, we calculated a diagnostic score for Legionella CAP. The median score was significantly higher in Legionella CAP as compared to patients without Legionella (4 (IQR 3-4) vs 2 (IQR 1-2), p < 0.0001) with a respective odds ratio of 3.34 (95%CI 2.57-4.33, p < 0.0001). Receiver operating characteristics showed a high diagnostic accuracy of this diagnostic score (AUC 0.86 (95%CI 0.81-0.90), which was better as compared to each parameter alone. Of the 191 patients (42%) with a score of 0 or 1 point, only 3% had Legionella pneumonia. Conversely, of the 73 patients (16%) with > or =4 points, 66% of patients had Legionella CAP. CONCLUSION: Six clinical and laboratory parameters embedded in a simple diagnostic score accurately identified patients with Legionella CAP. If validated in future studies, this score might aid in the management of suspected Legionella CAP.

Molecular evidence of interhuman transmission in an outbreak of Pneumocystis jirovecii pneumonia among renal transplant recipients.

S. Gianella, L. Haeberli, B. Joos, B. Ledergerber, R.P. Wüthrich, R. Weber, H. Kuster, P.M. Hauser, T. Fehr, N.J. Mueller. Molecular evidence of interhuman transmission in an outbreak of Pneumocystis jirovecii pneumonia among renal transplant recipients. Transpl Infect Dis 2009. All rights reserved Abstract: Pneumocystis jirovecii pneumonia (PCP) remains an important cause of morbidity and mortality in immunocompromised individuals. The epidemiology and pathogenesis of this infection are poorly understood, and the exact mode of transmission remains unclear. Recent studies reported clusters of PCP among immunocompromised patients, raising the suspicion of interhuman transmission. An unexpected increase of the incidence of PCP cases in our nephrology outpatient clinic prompted us to conduct a detailed analysis. Genotyping of 7 available specimens obtained from renal transplant recipients was performed using multi-locus DNA sequence typing (MLST). Fragments of 4 variable regions of the P. jirovecii genome (ITS1, 26S, mt26S, beta-tubulin) were sequenced and compared with those of 4 independent control patients. MLST analysis revealed identical sequences of the 4 regions among all 7 renal allograft recipients with available samples, indicating an infection with the same P. jirovecii genotype. We observed that all but 1 of the 19 PCP-infected transplant recipients had at least 1 concomitant visit with another PCP-infected patient within a common waiting area. This study provides evidence that nosocomial transmission among immunocompromised patients may have occurred in our nephrology outpatient clinic. Our findings have epidemiological implications and suggest that prolonged chemoprophylaxis for PCP may be warranted in an era of more intense immunosuppression.

Utilité du dosage de la CRP dans le diagnostic, le pronostic et le suivi de la pneumonie acquise dans la communauté [Role of C-reactive protein in the diagnosis, prognosis and follow-up of community-acquired pneumonia].

Community-acquired pneumonia (CAP) is a major clinical problem in terms of morbidity, mortality, and use of hospital resources. It is well recognized that a delay in making the diagnosis and instituting appropriate antibiotic treatment is associated with an increased mortality. C-reactive protein may be helpful in the management of patients with CAP. CRP is widely used in the management of CAP, including diagnosis, prognosis and follow-up. But its usefulness is not known. The aim of this systematic review was to evaluate the usefulness of CRP in the diagnosis, prognosis and follow-up of CAP.

Is the 23-valent pneumococcal polysaccharide vaccine useful in preventing community-acquired pneumonia?

Although bacteremic pneumococcal pneumonia is the most severe form of pneumonia, non-bacteremic forms are much more frequent. Laboratory methods for the diagnosis of nonbacteremic pneumococcal pneumonia have a low sensitivity and specificity, and therefore all-cause pneumonia has been proposed as a suitable outcome to evaluate vaccination effectiveness. This work reviews the epidemiology of community-acquired pneumonia (CAP) and evaluates the effectiveness of the 3-valent pneumococcal polysaccharide vaccine (PPV-23) in preventing CAP requiring hospitalization in people aged ≥65 years. We performed a case-control study in patients aged ≥65 years admitted through the emergency department who presented with clinical signs and symptoms compatible with pneumonia. Weincluded 489 cases and 1,467 controls and it was obtained a vaccine efectiveness of 23.6 (0.9-41.0). Our results suggest that PPV-23 vaccination is effective and reduces hospital admissions due to pneumonia in the elderly, strengthening the rationale for vaccination programmes in this age group.

Pneumocystis jirovecii genotype associated with increased death rate of HIV-infected patients with pneumonia.

Pneumocystis jirovecii dihydropteroate synthase (DHPS) mutations have been associated with failure of sulfa prophylaxis; their effect on the outcome of patients with P. jirovecii pneumonia (PCP) remains controversial. P. jirovecii DHPS polymorphisms and genotypes were identified in 112 cases of PCP in 110 HIV-infected patients by using PCR single-strand conformation polymorphism. Of the 110 patients observed, 21 died; 18 of those deaths were attributed to PCP. Thirty-three percent of the PCP cases involved a P. jirovecii strain that had 1 or both DHPS mutations. The presence or absence of DHPS mutations had no effect on the PCP mortality rate within 1 month, whereas P.jirovecii type 7 and mechanical ventilation at PCP diagnosis were associated with an increased risk of death caused by PCP. Mechanical ventilation at PCP diagnosis was also associated with an increased risk of sulfa treatment failure at 5 days.

Prise en charge de la pneumonie communautaire [Management of community acquired pneumonia]

Une grande partie des patients présentant une pneumonie communautaire ont un bon pronostic et peuvent être suivis dans la pratique ambulatoire moyennant un nombre limité d'examens paracliniques. Le diagnostic repose sur une clinique suggestive en présence d'un infiltrat compatible avec une pneumonie à la radiographie de thorax. Une anamnèse de voyage et une bonne connaissance de résistances locales du pneumocoque aux antibiotiques sont déterminantes pour le choix du traitement. Pour les patients de moins de 50 ans sans comorbidités et sans signes de sévérité, il est généralement recommandé de prescrire un macrolide ou une fluoroquinolone de 3e ou de 4e génération (fluoroquinolones «respiratoires»). Pour les patients plus âgés, et pour ceux qui présentent des comorbidités ou des critères de sévérité, une évaluation à l'hôpital est indiquée. La majorité des patients hospitalisés en soins généraux peuvent être traités par l'association d'une bêta-lactame et d'un macrolide, ou par une fluoroquinolone «respiratoire» seule, après prélèvements d'expectorations et de sang pour culture.

Pseudomonas aeruginosa serotypes in nosocomial pneumonia: prevalence and clinical outcomes.

INTRODUCTION: Pseudomonas aeruginosa frequently causes nosocomial pneumonia and is associated with poor outcome. The purpose of this study was to assess the prevalence and clinical outcome of nosocomial pneumonia caused by serotype-specific P. aeruginosa in critically ill patients under appropriate antimicrobial therapy management. METHODS: A retrospective, non-interventional epidemiological multicenter cohort study involving 143 patients with confirmed nosocomial pneumonia caused by P. aeruginosa. Patients were analyzed for a period of 30 days from time of nosocomial pneumonia onset. Fourteen patients fulfilling the same criteria from a phase IIa studyconducted at the same time/centers were included in the prevalence calculations but not in the clinical outcome analysis. RESULTS: The prevalence of serotypes was: O6 (29%), O11 (23%), O10 (10%), O2 (9%), and O1 (8%). Serotypes with a prevalence of less than 5% were found in 13% of patients, 8% were classified as not typeable. Across all serotypes, 19% mortality, 70% clinical resolution, 11% clinical continuation, and 5% clinical recurrence were recorded. Age and higher APACHE II (Acute Physiology and Chronic Health Evaluation II) were predictive risk factors associated with probability of death and lower clinical resolution for P. aeruginosa nosocomial pneumonia. Mortality tends to be higher with O1 (40%) and lower with O2 (0%); clinical resolution tends to be better with O2 (82%) compared to other serotypes. Persisting pneumonia with O6 and O11 was, respectively, 8% and 21%; clinical resolution with O6 and O11 was, respectively, 75% and 57%. CONCLUSIONS: In P. aeruginosa nosocomial pneumonia, the most prevalent serotypes were O6 and O11. Further studies including larger group sizes are needed to correlate clinical outcome with virulence factors of P. aeruginosa in patients with nosocomial pneumonia caused by various serotypes; and to compare O6 and O11, the two serotypes most frequently encountered in critically ill patients.

Heart failure and community-acquired pneumonia: cases for home hospital?

BACKGROUND: Home hospital is advocated in many western countries in spite of limited evidence of its economic advantage over usual hospital care. Heart failure and community-acquired pneumonia are two medical conditions which are frequently targeted by home hospital programs. While recent trials were devoted to comparisons of safety and costs, the acceptance of home hospital for patients with these conditions remains poorly described. OBJECTIVE: To document the medical eligibility and final transfer decision to home hospital for patients hospitalized with a primary diagnosis of heart failure or community-acquired pneumonia. DESIGN: Longitudinal study of patients admitted to the medical ward of acute care hospitals, up to the final decision concerning their transfer. SETTING: Medical departments of one university hospital and two regional teaching Swiss hospitals. PATIENTS: All patients admitted over a 9 month period to the three settings with a primary diagnosis of heart failure (n= 301) or pneumonia (n=441). MEASUREMENTS: Presence of permanent exclusion criteria on admission; final decision of (in)eligibility based on medical criteria; final decision regarding the transfer, taking into account the opinions of the family physician, the patient and informal caregivers. RESULTS: While 27.9% of heart failure and 37.6% of pneumonia patients were considered to be eligible from a medical point of view, the program acceptance by family physicians, patients and informal caregivers was low and a transfer to home hospital was ultimately chosen for just 3.8% of heart failure and 9.6% of pneumonia patients. There were no major differences between the three settings. CONCLUSIONS: In the case of these two conditions, the potential economic advantage of home hospital over usual inpatient care is compromised by the low proportion of patients ultimately transferred.

Pneumocystis-carinii-Pneumonie bei Säuglingen mit vertikaler HIV-Infektion in der Schweiz [Pneumocystis carinii pneumonia in infants with vertically acquired HIV infection in Switzerland]

OBJECTIVE: Review of incidence, clinical picture, therapy, and outcome of Pneumocystis carinii pneumonia (PCP) in infants with vertically-acquired HIV infection in Switzerland. METHODS: Inquiry among members of the Swiss Pediatrics AIDS Group, review of the data base of the Swiss Neonatal HIV Study and retrospective analysis of the charts from infants with PCP. RESULTS: Since 1986 PCP has been diagnosed in 10 out of 107 infants with vertically-acquired HIV infection. PCP occurred in 7 infants at the age of 3-6 months and in 3 at the age of 9-11 months. 4 infants showed symptoms related to HIV infection before developing PCP. Before the development of PCP, infection with HIV had been ascertained in 6 infants. In 2 the diagnosis was still unclear and in the 2 remaining the risk of HIV infection was not known. None of the infants was on primary prophylaxis against PCP. Signs and symptoms of PCP included cough and tachypnea (100%) as well as high fever up to 40 degrees C (90%). Transcutaneous oxygen saturation was 70-95%. Chest X-rays revealed interstitial infiltrates in 6 infants, localized infiltrates in 2 and interstitial as well as localized infiltrates in 2. The CD4+ cell count was, with one exception, < 1500/microliters, i.e. below the normal value for age. Side effects of high dose cotrimoxazole were noted in 6 patients. 5 infants required intubation and mechanical ventilation. 4 infants died due to PCP, including 3 of those who required intubation and mechanical ventilation. CONCLUSIONS: PCP in infants with vertically-acquired HIV infection preferentially occurs at the age of 3 to 6 months and is often lethal, especially in patients requiring intubation. Evaluation for HIV infection should be done as early as possible in order to introduce primary PCP prophylaxis in infants at risk for this opportunistic infection.

Fastidious intracellular bacteria as causal agents of community-acquired pneumonia.

Intracellular bacteria are common causes of community-acquired pneumonia that grow poorly or not at all on standard culture media and do not respond to beta-lactam antibiotic therapy. Apart from well-established agents of pneumonia such as Legionella pneumophila, Mycoplasma pneumoniae, Chlamydia pneumoniae, Chlamydia psittaci and Coxiella burnetii, some new emerging pathogens have recently been recognized, mainly Parachlamydia acanthamoebae and Simkania negevensis, two Chlamydia-related bacteria. Most of them are causes of benign and self-limited infections. However, they may cause severe pneumonia in some cases (i.e., Legionnaires' disease) and they may cause outbreaks representing a public health problem deserving prompt recognition and appropriate therapy. Although extrapulmonary manifestations are often present, no clinical features allow them to be distinguished from classical bacterial agents of pneumonia such as Streptococcus pneumoniae. Thus, specific molecular diagnostic tools are very helpful for early recognition of the offending bacteria, whereas serology often only allows retrospective or late diagnosis. Macrolides remain the best empirical treatment of intracellular respiratory pathogens, although some observational studies suggest that quinolones may be superior for the treatment of legionellosis.