Treatment of community-acquired pneumonia. / Behandling av pneumoni oppstått utenfor sykehus.

BAKGRUNN: Helsedirektoratet gir ut nasjonale retningslinjer for antibiotikabruk i sykehus. For pneumoni oppstått utenfor sykehus anbefales penicillin ved mild til moderat pneumoni og penicillin i kombinasjon med gentamicin ved alvorlig pneumoni. Alvorlighetsgrad vurderes med CRB-65-kriteriene. Vi vet lite om etterlevelse av retningslinjene. METODE: Vi gjennomgikk journalene til pasienter innlagt med pneumoni med Streptococcus pneumoniae eller Haemophilus influenzae ved Infeksjonsmedisinsk avdeling ved Oslo universitetssykehus, Ullevål sykehus, i 2015 (N = 70) og undersøkte om behandlingen som ble gitt, var i samsvar med de nasjonale retningslinjene. RESULTATER: 24 (34 %) av pasientene fikk penicillin i monoterapi, 25 (36 %) fikk kombinasjonen penicillin og gentamicin, 14 (20 %) fikk kefalosporiner, mens 7 (10 %) fikk andre antibiotika. Totalt fikk 38 (54 %) pasienter empirisk antibiotika i henhold til retningslinjene. CRB-65-kriteriene ble ikke dokumentert hos noen av pasientene. 38 av 50 pasienter som fikk penicillin, fikk høyere doser enn anbefalt. 62 (89 %) pasienter fikk justert behandling etter at bakteriesvar forelå. Median lengde av antibiotikabehandling var 10 døgn (interkvartilintervall 8-11 døgn). FORTOLKNING: Bredspektrede antibiotika ble benyttet oftere enn retningslinjene skulle tilsi. Etter at bakteriesvar forelå, ble behandlingen justert i henhold til de nasjonale retningslinjene. Penicillindosene var ofte for høye og behandlingslengden for lang sammenholdt med de nasjonale retningslinjene.

Low Serum Fetuin-A as a Biomarker to Predict Pneumococcal Necrotizing Pneumonia and Hemolytic Uremic Syndrome in Children.

Streptococcus pneumoniae, a neuraminidase-producing pathogen, can cause invasive pneumococcal disease (IPD) with or without hemolytic uremic syndrome (HUS) in humans. We aimed to identify serum sialoglycoproteins that are targeted by neuraminidases in severe pneumococcal infection. We hypothesized that serum sialoglycoprotein such as fetuin-A can serve as a biomarker to predict IPD or HUS. We constructed serum sialoglycoprotein profiles before and after pneumococcal neuraminidase treatment using liquid chromatography-tandem mass spectrometry (LC-MS/MS), a proteomic approach. An observational study was conducted using clinical data and serum samples from pediatric patients with pneumococcal infection to verify the predictive role of fetuin-A in IPD. Serum fetuin-A levels were determined by enzyme-linked immunosorbent assay. The most abundant serum sialoglycoproteins identified by LC-MS/MS after neuraminidase treatment and peanut lectin capture were immunoglobulins, apolipoproteins, fibrinogens, keratins, complement system proteins, and fetuin-A. Serum fetuin-A levels in the HUS patients were significantly lower (207 ±â€Š80 mg/L, P < 0.001) than in patients with lobar pneumonia (610 ±â€Š190 mg/L) as well as the healthy controls (630 ±â€Š250 mg/L). In comparing HUS with necrotizing pneumonia and lobar pneumonia, the ROC area under the curve was 0.842; a cutoff value of 298 mg/L yielded sensitivity of 92.9% (95% CI: 68.5-98.7%) and specificity of 71.9% (95% CI: 54.6-84.4%). This observational study with validation cohorts of patients with HUS, complicated pneumonia, and lobar pneumonia demonstrates the high performance of low serum fetuin-A levels as a biomarker to predict severe IPD and HUS in children.

[A-DROP system might result in underestimation of severity of cases with Legionnaires' disease].

Fifteen cases of legionella pneumonia experienced in our department or associated hospital were included in this study. Each case was classified with the A-DROP system of the Japanese Respiratory Society Guidelines, and guidelines from the Infectious Diseases Society of America (IDSA) (1998) and then we compared the severity of the cases of pneumonia. Although 10 cases were classified as intermediate, 3 as severe, and 2 as extremely severe with the A-DROP system, most cases were classified as severe according to the IDSA guidelines. Among 5 fatal cases, three were ranked as intermediate with the A-DROP system. However all the fatal cases were ranked as severe in the IDSA guidelines. This study suggested that the A-DROP system might underestimate the severity of pneumonia in cases with legionella pneumonia.

Establishment of a young mouse model and identification of an allelic variation of zmpB in complicated pneumonia caused by Streptococcus pneumoniae.

OBJECTIVE: Complicated pneumonia, including necrotizing pneumonia, lung abscess, and empyema, caused by Streptococcus pneumoniae in children has been increasing. We thus determined to investigate its virulence in an animal model and to identify virulence factors of S. pneumoniae. DESIGN: Prospective, randomized, controlled animal study. SETTING: University medical laboratory. SUBJECTS: Male Balb/c-strain mice, 3 wks old. INTERVENTIONS: We used a young mouse model to monitor bacterial virulence and a microarray to compare gene expression between S. pneumoniae from children with complicated and noncomplicated pneumonia. Deletion and complementation of a candidate gene were performed to study its role on the virulence of S. pneumoniae. MEASUREMENTS AND MAIN RESULTS: A model of complicated pneumonia in young mice infected with strains of S. pneumoniae from children with complicated pneumonia was established. Using a microarray analysis, differences in zinc metalloprotease B (zmpB) RNA hybridization between two strains from children with complicated pneumonia (NTUH-p28 and NTUH-p15) and a strain (NTUH-p3) from a child with pneumococcal lobar pneumonia were found. Confirmatory assays revealed the signal differences were due to sequence variation in the zmpB gene. Infection with the zmpB deletion mutant of NTUH-p15 showed a significant decrease in the severity of pneumonia and no destructive lung injury. The zmpB complementation strain of NTUH-p15 significantly restored the level of inflammation and caused lung necrosis. For studying the effect of allelic variation of zmpB on the virulence of S. pneumoniae, we added zmpB of NTUH-p15 in the zmpB deletion mutant of NTUH-p3, which resulted in a higher bacterial burden than that in wild-type NTUH-p3. CONCLUSIONS: A young mouse model is established for complicated pneumococcal pneumonia. This model proved that allelic variation of zmpB affects the virulence of S. pneumoniae.

Changing epidemiology of pneumococcal meningitis after the introduction of pneumococcal conjugate vaccine in the United States.

BACKGROUND: Although hospitalizations due to invasive pneumococcal disease decreased after routine vaccination of young children with a 7-valent pneumococcal conjugate vaccine (PCV7) began in 2000, information on the trends in pneumococcal meningitis is limited. METHODS: We estimated national trends in rates of hospitalization for pneumococcal meningitis, using data from the Nationwide Inpatient Sample, 1994-2004. Pneumococcal meningitis cases and deaths were identified on the basis of the International Classification of Diseases, Ninth Edition, Clinical Modification coded primary discharge diagnosis, and rates were calculated using US Census data as denominators. The year 2000 was considered to be a transition year, and the average annualized rate after PCV7 introduction (2001-2004) was compared with that during the baseline years (1994-1999). RESULTS: During 1994-2004, there were 21,396 hospitalizations and 2684 deaths (12.5%) due to pneumococcal meningitis in the United States. In children aged < 2 years, the average annualized rates of pneumococcal meningitis hospitalizations per 100,000 population decreased from 7.7 in 1994-1999 to 2.6 in 2001-2004 (change, -66.0%; 95% confidence interval [CI], -73.5% to -56.3%). Among children aged 2-4 years, the hospitalization rate decreased from 0.9 to 0.5 per 100,000 (change, -51.5%; 95% CI, -66.9% to -28.9%). Average rates also decreased by 33.0% (95% CI, -43.4% to -20.9%) among adults aged > or = 65 years. After PCV7 introduction (2001-2004), an estimated 1822 and 573 pneumococcal meningitis hospitalizations were prevented in persons aged < 5 years and > or = 65 years, respectively. Overall, an estimated 3330 pneumococcal meningitis hospitalizations and 394 deaths were prevented in persons of all ages during 2001-2004 in the United States. CONCLUSION: After implementation of routine childhood vaccination with PCV7, hospitalizations for pneumococcal meningitis decreased significantly for both children and adults. Most pneumococcal meningitis cases now occur among adults.

International classification of diseases codes showed modest sensitivity for detecting community-acquired pneumonia.

OBJECTIVE: To estimate the sensitivity of International Classification of Diseases (ICD-9-CM) coding for detecting hospitalized community-acquired pneumonia and to assess possible determinants for misclassification. STUDY DESIGN AND SETTING: Based on microbiological analysis data, 293 patients with a principal diagnosis of community-acquired pneumonia at seven hospitals in the Netherlands were assigned to three categories (pneumococcal pneumonia, pneumonia with other organism, or pneumonia with no organism specified). For these patients, the assigned principal and secondary ICD-9-CM codes in the hospital discharge record were retrieved and the corresponding sensitivity was calculated. Furthermore, pneumonia-related patient characteristics were compared between correctly and incorrectly coded subjects. RESULTS: The overall sensitivity was 72.4% for the principal code and 79.5% for combined principal and secondary codes. For pneumococcal pneumonia (ICD-9-CM code 481) and pneumonia with specified organism (ICD-9-CM code 482-483), the sensitivities were 35% and 18.3%, respectively. Patient characteristics were not significantly different between correctly and incorrectly coded subjects except for duration of hospital stay, which correlated negatively with coding sensitivity (P=0.01). CONCLUSION: ICD-9-CM codes showed modest sensitivity for detecting community-acquired pneumonia in hospital administrative databases, leaving at least one quarter of pneumonia cases undetected. Sensitivity decreased with longer duration of hospital stay.

Sepsis severity predicts outcome in community-acquired pneumococcal pneumonia.

Easily performed prognostic rules are helpful for guiding the intensity of monitoring and treatment of patients. The aim of the present study was to compare the predictive value of the sepsis score and the Confusion, Respiratory rate (> or =30 breaths.min(-1)), Blood pressure (systolic value <90 mmHg or diastolic value < or =60 mmHg) and age > or =65 yrs (CRB-65) score in 105 patients with community-acquired pneumococcal pneumonia. In addition, the influence of timing of the antimicrobial treatment on outcome was investigated. The sepsis and the CRB-65 scores were used to allocate patients to subgroups with low, intermediate and high risk. Comparable, highly predictive values for mortality were found for both scores (sepsis score versus CRB-65): 1) low-risk group, 0 versus 0%; 2) intermediate-risk group, 0 versus 8.6%; 3) high-risk group, 30.6 versus 40%, with an area under the curve of 0.867 versus 0.845. Patients with ambulatory antibiotic pre-treatment had less severe disease with a lower acute physiology score, lower white blood cell count and a faster decline of C-reactive protein levels. No pre-treated patient died. In summary, both scores performed equally well in predicting mortality. The prediction of survival in the intermediate-risk group might be more accurate with the sepsis score. Pre-hospital antibiotic treatment was associated with less severe disease.

Changing characteristics of invasive pneumococcal disease in Metropolitan Atlanta, Georgia, after introduction of a 7-valent pneumococcal conjugate vaccine.

BACKGROUND: The rate of invasive pneumococcal disease (IPD) has decreased among both immunized children and nonimmunized adults since the licensure of a heptavalent pneumococcal conjugate vaccine (PCV7) for use in infants in the United States in 2000. METHODS: Temporal trends in IPD incidence, clinical syndromes, and underlying conditions were analyzed using active laboratory- and population-based surveillance data from the Centers for Disease Control and Prevention-sponsored Georgia Emerging Infections Program for the 20-county Metropolitan Atlanta, Georgia, for the period of July 1997 through June 2004. P values were determined by test for trend. RESULTS: Since 2000, there have been significant decreases in the rates of invasive pneumococcal pneumonia (relative risk [RR], 0.80; P=.002) and meningitis (RR, 0.41; P=.003) in adults and for primary bacteremia, invasive pneumonia, and meningitis in children (RR, 0.16 [P<.001], 0.60 [P=.003], and 0.70 [P=.009], respectively). Among human immunodeficiency virus-infected persons, there were significant decreases in the overall rates of IPD (decrease of 43%; P<.001) and invasive pneumonia (decrease of 44%; P<.001) since 2000-2001, although the rate of IPD increased significantly (increase of 53%; P=.022) among patients with acquired immunodeficiency syndrome. There was a concurrent increase in the proportion of adults aged > or = 40 years with underlying comorbidities. Rates of non-PCV7 serotypes increased 1.61-fold and 1.28-fold from 2000-2001 to 2003-2004 in children and adults (P=.005 for both). CONCLUSIONS: The decreasing incidence of IPD in Atlanta since 2000-2001 was associated with decreases in cases of pneumonia and meningitis in adult and pediatric subjects and in cases of primary bacteremia in children. The burden of serotype-replacement disease remained small. Adults with comorbidities represent a growing proportion of patients with IPD.

Decline in pneumonia admissions after routine childhood immunisation with pneumococcal conjugate vaccine in the USA: a time-series analysis.

BACKGROUND: Routine infant immunisation with seven-valent pneumococcal conjugate vaccine (PCV7) began in the USA in 2000. Although invasive pneumococcal disease has declined substantially, the programme's effect on hospital admissions for pneumonia is unknown. We therefore assessed the effect of the programme on rates of all-cause and pneumococcal pneumonia admissions. METHODS: Data from the Nationwide Inpatient Sample, the largest inpatient database available in the USA, were analysed with an interrupted time-series analysis that used pneumonia (all-cause and pneumococcal) admission rates as the main outcomes. Monthly admission rates estimated for years after the introduction of PCV7 vaccination (2001-2004) were compared with expected rates calculated from pre-PCV7 years (1997-1999). The year of vaccine introduction (2000) was excluded, and rates of admission for dehydration were assessed for comparison. FINDINGS: At the end of 2004, all-cause pneumonia admission rates had declined by 39% (95% CI 22-52) for children younger than 2 years, who were the target population of the vaccination programme. This annual decline in all-cause pneumonia admissions of 506 (291-675) per 100,000 children younger than 2 years represented about 41,000 pneumonia admissions prevented in 2004. During the 8 study years, 10,659 (2%) children younger than 2 years admitted with pneumonia were coded as having pneumococcal disease; these rates declined by 65% (47-77). This decline represented about 17 fewer admissions per 100,000 children in 2004. Admission rates for dehydration for children younger than 2 years remained stable over the study period. INTERPRETATION: The reduction in all-cause pneumonia admissions in children younger than 2 years provides an estimate of the proportion of childhood pneumonias attributable to Streptococcus pneumoniae in the USA that are vaccine preventable. Our results contribute to the growing body of evidence supporting the beneficial effects of the pneumococcal conjugate vaccines in children.

[Community-acquired pneumonia--treatment perspectives in the physician's office]. / Behandlungsperspektiven der Pneumonie in der Praxis. Wettlauf mit den Resistenzen.

In patients with a focal finding on auscultation, a chest radiograph should be performed to confirm pneumonia. The need for hospitalization can be supported objectively with the aid of the Pulmonary Severity Index (PSI) or the CURB score. The most common pathogen of pneumonia is Streptococcus pneumoniae. The choice of appropriate antimicrobial therapy is based on the expected spectrum of pathogens, severity, the risk profile and the patient's history of antimicrobial substance use. In this connection, the progressive development of resistance forbids first-choice recommendations, and "cycling" should be attempted instead. Depending on the regional resistance situation and prior conditions, amoxicillin in combination with a beta-lactamase inhibitor, doxycycline, a macrolide or a ketolide may be considered for treatment purposes. For higher levels of severity, fluorquinolones also have proven value.

Community-acquired pneumonia: etiology, epidemiology, and outcome at a teaching hospital in Argentina.

OBJECTIVE: To survey the etiology and epidemiology of community-acquired pneumonia (CAP) in relation to age, comorbidity, and severity and to investigate prognostic factors. DESIGN: Prospective epidemiologic study, single center. SETTING: University hospital at Buenos Aires, Argentina. PATIENTS: Outpatients and inpatients fulfilling clinical criteria of CAP. INTERVENTIONS: Systematic laboratory evaluation for determining the etiology, and clinical evaluation stratifying patients into mild, moderate, and severe CAP (groups 1 to 3), a clinical rule used for hospitalization. RESULTS: During a 12-month period, 343 patients (mean age, 64.4 years; range, 18 to 102 years) were evaluated. We found 167 microorganisms in 144 cases (yield, 42%). Streptococcus pneumoniae, the most common pathogen, was isolated in 35 cases (24%). Mycoplasma pneumoniae, present in 19 (13%), was second in frequency in group 1; Haemophilus influenzae, present in 17 cases (12%), was second in group 2; and Chlamydia pneumoniae, present in 12 cases (8%), was second in group 3. Etiology could not be determined on the basis of clinical presentation; identifying the etiology had no impact on mortality. Some findings were associated with specific causative organisms and outcome. A significantly lower number of nonsurvivors received adequate therapy (50% vs 77%). CONCLUSIONS: Age, comorbidities, alcohol abuse, and smoking were related with distinct etiologies. PaO(2) to fraction of inspired oxygen ratio < 250, aerobic Gram-negative pathogen, chronic renal failure, Glasgow score < 15, malignant neoplasm, and aspirative pneumonia were associated with mortality by multivariate analysis. Local microbiologic data could be of help in tailoring therapeutic guidelines to the microbiologic reality at different settings. The stratification schema and the clinical rule used for hospitalization were useful.

Invasive pneumococcal infections in Canadian children, 1991-1998: implications for new vaccination strategies. Canadian Paediatric Society/Laboratory Centre for Disease Control Immunization Monitoring Program, Active (IMPACT).

We reviewed 2040 consecutive cases of invasive pneumococcal infection that were seen at 11 pediatric centers across Canada during 1991-1998 to determine if such infections could be prevented by new conjugate vaccines. Isolates from 1528 cases were serotyped. Most cases (61.5%) occurred in patients aged >2 years. Underlying medical conditions were present in 23.2% of case patients. Serotypes in the 7-valent conjugate vaccine matched isolates as follows: 85.8% of tested isolates from children aged 6 months to 5 years, but significantly fewer isolates in younger and older children; 72.9% of isolates from non-healthy children, but 83.9% of isolates from previously healthy children; and 95.4% of isolates with high-level penicillin resistance, but only 72.7% of those with intermediate-level resistance. Significant natural variation in the proportion of isolates matching 7-valent vaccines occurred from year to year and among centers. New conjugate vaccines have great potential but their effectiveness and limitations require ongoing study.

Epidemiological features and prognosis of severe community-acquired pneumococcal pneumonia.

OBJECTIVE: To describe risk factors of severe pneumococcal community-acquired pneumonia and to study variables influencing outcome. DESIGN: Retrospective (1987-1992) and prospective (1993-1995) study. SETTING: Three participating ICUs from primary care hospitals. PATIENTS: Five hundred and five patients (mean age: 63 +/- 17 years) with severe community-acquired pneumonia (CAP). Three groups of patients were defined: pneumococcal CAP (group 1), CAP with microbial diagnosis other than Streptococcus pneumoniae (group 2), CAP from group 2 and CAP without microbial diagnosis (group 3). MEASUREMENTS AND RESULTS: Admission data and data on the disease's course were recorded. The mean Simplified Acute Physiologic Score (SAPS) was 12.5 +/- 5.4. On admission 288 (57 %) patients were mechanically ventilated (mv) and 82 (16.2 %) required inotropic support. A microbial diagnosis was established for 309 (61.2%) patients. S. pneumoniae was isolated in 137 (27.1%) patients. Severe pneumococcal CAP was independently associated with male sex (p = 0.01), lack of antibiotics use before admission (p = 0.0001), non-aspiration pneumonia (p = 0.01) and septic shock (p = 0.0001). The overall mortality rate was 27.5 % (29.2 % in group 1). In patients with severe pneumococcal CAP, multivariate analysis showed that leukopenia less than 3,500/mm3 (p = 0.0004), age over 65 years (p = 0.01), septic shock (p = 0.01), sepsis related complications (p = 0.0001), ICU complications (p = 0.001) and inadequacy of antimicrobial therapy (p = 0.002) worsened the prognosis. CONCLUSIONS: Few features facilitate the identification of pneumococcal CAP on ICU admission. The prognosis is mostly related to severity of illness (leukopenia, septic shock) while comorbidities do not seem to influence outcome. Sepsis-related disorders, ICU complications and adequate antimicrobial chemotherapy are the major variables affecting the outcome during an ICU stay.

Accuracy of ICD-9-CM codes in detecting community-acquired pneumococcal pneumonia for incidence and vaccine efficacy studies.

Studies have used medical record discharge data as coded by the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) to estimate pneumococcal pneumonia incidence and vaccine efficacy. However, the accuracy of coding data to identify laboratory-confirmed pneumococcal pneumonia is not known. With the use of information collected in Ohio for a community-based pneumonia incidence study, the authors calculated the sensitivities, specificities, positive predictive values (PPV), and negative predictive values (NPV) of specific codes for pneumococcal pneumonia among hospitalized patients with community-acquired pneumonia. Sensitivities of the most common ICD-9-CM codes listed in the first five positions for patients with laboratory-confirmed pneumococcal pneumonia were 58.3% (code 481.0, pneumococcal pneumonia), 20.4% (38.0, streptococcal septicemia), 19.2% (38.2, pneumococcal septicemia), 15.0% (518.81, respiratory failure), 14.2% (486.0, pneumonia, organism unspecified), and 11.3% (482.3, streptococcal pneumonia). Using the first five listed ICD-9-CM codes rather than just the first listed code increased sensitivity without causing substantial change in specificity, PPV, and NPV. Sensitivity, PPV, and NPV of individual and groups of codes varied with different case definitions of pneumococcal pneumonia. Incidence and vaccine efficacy studies with the ability to validate diagnoses by medical chart review can use a combination of many ICD-9-CM codes to maximize sensitivity. However, without the ability to review medical charts, researchers must carefully decide which codes would best suit their studies.

Pneumococcal antigen persistence in sputum from patients with community-acquired pneumonia.

The purpose of this study was to establish the diagnostic value of pneumococcal capsular antigen by comparing this with the results of Gram stain and culture in representative and nonrepresentative sputa during follow-up in patients with community-acquired pneumonia. Antigen was detected by a latex particle agglutination test. At the time of hospital admission, antigen was detected in 17 representative sputum specimens from 30 patients with pneumococcal pneumonia, which was comparable to the results of Gram stain and culture. In five additional patients, antigen was demonstrated in nonrepresentative specimens. During follow-up under antibiotic treatment, this number increased by six: three patients with representative and three patients with nonrepresentative sputum, respectively. Two of the 22 patients with pneumonia of other known cause had an antigen-positive sputum on admission and in another two patients, sputum antigen was detected during follow-up. Ten of 34 patients with pneumonia of unknown cause had detectable antigen in representative or nonrepresentative sputum on admission. During follow-up, antigen was detected in sputa of an additional seven patients. There was no difference in duration of antigen persistence between patients with pneumococcal pneumonia and pneumonia of unknown cause. It was observed that the first antigen-positive sputum specimen was always detected within the first five days of the hospital stay. We conclude that antigen detection in both representative and nonrepresentative sputum specimens at the time of hospital admission and during follow-up is of additional value for the diagnosis of pneumococcal pneumonia. It markedly increases the number of patients with pneumococcal pneumonia detected, who would otherwise be considered to have pneumonia of unknown cause. However, antigen-positive results should be interpreted carefully, especially in those pneumonia patients with chronic bronchitis, because detectable antigen may be caused by pneumococcal carriership of the lower respiratory tract.