Devora Lieberman

Pneumonic vs nonpneumonic acute exacerbations of COPD

Study objective To describe and compare the background, clinical manifestations, disease course, and infectious etiologies of pneumonic acute exacerbations (PNAE) vs nonpneumonic acute exacerbations (NPAE) of COPD. Design A prospective, observational study. Setting A tertiary university medical center in southern Israel. Patients Twenty-three hospitalizations for PNAE and 217 hospitalizations for NPAE were included in the study. Paired sera were obtained for each of the hospitalizations and were tested serologically for 12 pathogens. Only a significant change in antibody titers or levels was considered diagnostic. Results No significant differences were found between the two groups for any of the parameters related to COPD or comorbidity. The clinical type of the exacerbation was not significantly different between the groups. Compared to NPAE, patients with PNAE had lower Po 2 values at hospital admission (p = 0.004) but higher rates of abrupt onset (p = 0.005), ICU admissions (p = 0.006), invasive mechanical ventilation (p = 0.01), mortality (p = 0.007), and longer hospital stay (p = 0.001). In 22 PNAE hospitalizations (96%) and in 153 NPAE hospitalizations (71%), at least one infectious etiology was identified (p = 0.001). Mixed infection was found in 13 patients with PNAE (59%) and in 59 patients with NPAE (39%; not significant [NS]). Viral etiology was identified in 18 patients with PNAE (78%) compared with 99 patients with NPAE (46%; p = 0.003). Pneumococcal etiology was found in 10 patients with PNAE (43%) and in 38 patients with NPAE (18%; p = 0.006). An atypical etiology was identified in 8 patients with PNAE (35%) and 64 patients with NPAE (30%; NS). Conclusions Community-acquired pneumonia is common among patients hospitalized for an acute exacerbation of COPD and is generally manifested by more severe clinical and laboratory parameters. In PNAE, compared to NPAE, viral and pneumococcal etiologies are more common, but the rate of atypical pathogens is similar. The therapeutic significance of these findings should be investigated further.

Respiratory Viruses in Adults With Community-Acquired Pneumonia

Background Use of nucleic acid amplification techniques has increased the identification of respiratory viruses (RVs) in adult patients with community-acquired pneumonia (CAP). The objectives of the present study were to identify RV in patients with CAP using three different sampling methods and to compare CAP virus proportions and types with two comparison groups. Methods The study population included 183 adult patients with CAP, 450 control subjects, and 201 patients with nonpneumonic lower respiratory tract infection (NPLRTI). Each participant was sampled by oropharyngeal swab, nasopharyngeal swab, and nasopharyngeal washing, and the samples were tested for detection of 12 RVs by multiplex TaqMan Hydrolysis probe-based real-time polymerase chain reaction (Integrated DNA Technology; Coralville, IA). Results At least one RV was identified in 58 patients with CAP (31.7%) compared with 32 (7.1%) in control subjects and 104 (51.7%) in patients with NPLRTI (P < .01 and P < .01, respectively). Coronaviruses were identified in 24 (13.1%) patients with CAP, compared with 17 (3.8%) in control subjects, and 21 (10.4%) patients with NPLRTI. Respiratory syncytial virus was identified in 13 (7.1%), four (0.9%), and seven (3.5%); rhinovirus in nine (4.9%), nine (2.0%), and 15 (7.5%); and influenza virus in eight (4.4%), two (0.4%), and 63 (31.3%) patients with CAP, control subjects, and patients with NPLRTI, respectively. Conclusions The proportion of RV involvement in CAP is higher than previously reported. The proportion of RV identified in healthy subjects is significantly lower than in CAP, but it is not zero and should be weighed when interpreting corresponding proportions among patients.

Infectious etiologies in acute exacerbation of COPD

Acute exacerbation (AE) is a frequent episode during the prolonged chronic course of chronic obstructive pulmonary disease (COPD), which entails significant morbidity and mortality. The purpose of this study was to determine the frequency distribution of infectious etiologies in these episodes. Two hundred forty hospitalizations for AECOPD were included in a prospective, purely serologically based study. Paired sera were obtained for each of the hospitalizations and were tested using immunofluorescence or EIA methods to identify 13 different pathogens. Only significant changes in antibody titers were considered diagnostic. The mean age ( +/- SD) of the patients was 66.8 +/- 9.0 years and 179 (84%) were males. In 175 (72.9%) hospitalizations at least one infectious etiology was identified. In 117 (48.8%) hospitalizations at least one of 7 viral etiologies was identified. In 72 (30.0%) hospitalizations at least one of the following atypical bacteria was identified: Legionella spp. in 40 (16.7%), Mycoplasma pneumoniae in 34 (14.2%), and Coxiella burnetii in a single hospitalization. In 58 (24.2%) hospitalizations at least one classic bacterial etiology was found: Streptococcus pneumoniae in 48 (20.0%), Hemophilus influenzae in 10 (4.2%) and Moraxella catarrhalis in 9 (3.8%). More than one etiology was found in 72 (30.0%) hospitalizations. There were no significant differences in the etiologic distribution when the patients were classified by severity of airway obstruction or the clinical type of the exacerbation. We conclude that in most cases of hospitalization due to AECOPD the infectious etiology is viral or atypical bacteria and is classic bacteria in only a minority of cases. More than one etiologic cause can be identified in a third of the cases. The frequency distribution of the etiologies is not associated with the severity of airway obstruction or the clinical type of the exacerbation. The results of our study suggest that atypical bacteria should be covered in antibiotic regimens recommended for AECOPD. This issue should be addressed in future studies.

Identification of Respiratory Viruses in Adults: Nasopharyngeal versus Oropharyngeal Sampling

ABSTRACT The optimal method for identifying respiratory viruses in adults has not been established. The objective of the study was to compare the sensitivities of three sampling methods for this purpose. One thousand participants (mean age, 63.1 ± 17.8 years) were included. Of these, 550 were patients hospitalized for acute febrile lower respiratory tract infections and 450 were controls. Oropharyngeal swabs (OPS), nasopharyngeal swabs (NPS), and nasopharyngeal washings (NPW) were obtained from each participant and were tested for 12 respiratory viruses by a multiplex hydrolysis probes-based quantitative real-time reverse transcription-PCR. Patients were defined as positive for a specific virus if the virus was identified by at least one sampling method. In all, 251 viruses were identified in 244 participants. For the detection of any virus, the sensitivity rates for OPS, NPS, and NPW were 54.2%, 73.3%, and 84.9%, respectively (for OPS versus NPS and NPW, P < 0.00001; for NPS versus NPW, P < 0.003). Maximal sensitivity was obtained only with sampling by all three methods. The same gradation of sensitivity for the three sampling methods was found when influenza viruses, coronaviruses, and rhinoviruses were analyzed separately. The three sampling methods yielded equal sensitivity rates for respiratory syncytial virus. We conclude that nasopharyngeal sampling has a higher rate of sensitivity than oropharyngeal sampling and that the use of NPW has a higher rate of sensitivity than the use of NPS with a rigid cotton swab for the identification of respiratory viruses in adults. Sampling by all three methods is required for the maximal detection of respiratory viruses.

The epidemiology of community-acquired pneumonia among hospitalized adults

OBJECTIVE To identify and characterize the aetiological agents of community-acquired pneumonia (CAP) among hospitalized patients, as an aid in therapeutic decision-making. METHOD A prospective 1 year study of all patients hospitalized with CAP in the Negev region of Israel. The aetiology was determined by blood and pleural fluid cultures, and specific serological testing for pathogenic agents. Eighty-nine percent of the patients underwent follow-up for a month after discharge. RESULTS The study included 346 patients (53% males, mean age 49.3 +/- 19.5, range 17-94). A single aetiologic agent was identified in 146 patients (42.2%), multiple agents were found in 133 (38.4%), and no agent was identified in 67 (19.4%). Among the common pathogens were Pneumococcus sp. in 148 patients (42.8%). Mycoplasma pneumoniae (101, 29.2%), Chlamydia pneumoniae (62, 17.9%), Legionella sp. (56, 16.2%), viruses (35, 10.1%), Coxiella burnetti (20, 5.8%). Haemophilus influenzae (19, 5.5%), and other bacteria (21, 6.1%). Approximately 70% of the patients infected with M. pneumoniae and C. burnetti were younger than 45 years (P < 0.05). In contrast, about 50% of the patients with C. pneumoniae (TWAR) were over the age of 65 (P = 0.03). The presence of comorbidity was associated with a greater frequency of bacterial aetiologies (57% vs. 44%, P = 0.02), and fewer infections with M. pneumoniae (15% vs. 36%, P = 0.0004), or C. burnetii (2% vs. 8%, P = 0.02). Specific causative agents were associated with specific seasons: viruses between December and April (P = 0.03), and Legionella sp. from July to October (P = 0.003). In contrast, no seasonal variation was associated with pneumococcus, M. pneumoniae, or C. pneumoniae (TWAR). CONCLUSIONS Patients are hospitalized with CAP throughout the year. Since the pathogen is usually unknown at hospitalization, epidemiological data is important for choosing medication. The findings of this study point to the importance of macrolides alone or in combination with cephalosporins, as the treatment of choice for patients in our region.

Serological evidence of Mycoplasma pneumoniae infection in acute exacerbation of COPD.

A prospective study was conducted to identify and characterize hospitalizations for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with serologic evidence of infection with Mycoplasma pneumoniae (Mp). Two hundred forty hospitalizations for AECOPD were included in a 17-month prospective study. Paired sera were obtained for each of the hospitalizations and were tested serologically for Mp using a commercial enzyme immunoassay (EIA) kit. Only significant changes, according to the formula in the manufacturers instructions, in antibody titers for IgM and/or IgG and/or IgA were considered diagnostic for Mp infection. In 34 hospitalizations (14.2%) the serologic tests for Mp were positive (MpH). In 29 of these hospitalizations (85%) a significant change in IgA was found. In 11 of these hospitalizations (32%) the only change identified was in IgA. In 24 MpH (71%) there was serologic evidence for infection with at least one other respiratory pathogen. In comparison to the 206 hospitalizations without serologic evidence of infection with Mp, MpH had higher rates of inhaled steroid therapy (41% vs. 24%, p = 0.033) and a longer time interval between the appearance of dyspnea and hospitalization (6.6 +/- 3.8 days vs. 5.0 +/- 3.5 days, p = 0.012). There were no significant differences between these two groups in a broad spectrum of patient- and exacerbation-related clinical variables. Specific antibiotic therapy for Mp in the MpH group did not shorten the hospital stay. Serologic evidence of Mp infection is common in patients hospitalized for AECOPD, and is usually based on changes in specific IgA antibody titers. In most MpH another respiratory pathogen can be identified. The vast majority of clinical characteristics are the same in patients with and without serologic evidence of infection with Mp. The practical implications of these findings should be clarified in further studies.

Factors related to successful rehabilitation after hip fracture: a case—control study

A case-control study was performed to evaluate factors associated with successful rehabilitation in elderly patients who sustained hip fractures. All 170 patients with fractured hips hospitalized in the geriatrics ward of the Soroka Medical Center in Beer-Sheva, Israel between 1987 and 1991 were studied. Success of rehabilitation was determined by staff evaluation of the patients ability to walk and perform activities of daily living. The independent variables, including sociodemographic and medical variables, and mental and functional assessments, were assessed by chart reviews, staff evaluation and mental tests. One-hundred and twenty-nine patients (75.9%) were successfully rehabilitated. A normal mental state (p < 0.0001), female gender (p < 0.02) and absence of diabetes mellitus (p < 0.008) were associated significantly with successful rehabilitation.

Chlamydia pneumoniae community-acquired pneumonia: A review of 62 hospitalized adult patients

SummaryIn a prospective study,Chlamydia pneumoniae was identified as the etiological agent in 62 (17.9%) of 346 adult patients hospitalized over the course of one year for community-acquired pneumonia at the Soroka Medical Center in Beer-Sheva, Israel. The diagnosis ofC. pneumoniae infection was based on serological testing of antibodies by the MIF technique. In 43 of these patients (69.4%), at least one other etiological agent, in addition toC. pneumoniae for community-acquired pneumonia was identified.Streptococcus pneumoniae was identified in 34 patients withC. pneumoniae (54.8%), as an additional causative factor in infection. Community-acquired pneumonia patients withC. pneumoniae were significantly older than non-C. pneumoniae patients (p=0.03), had a higher APACHE II score on admission (p<0.05), a higher rate of positive blood cultures (p=0.02), and longer periods of hospitalization (p=0.022). Seven patients with pureC. pneumoniae infection recovered, despite treatment which is not considered to be specific forC. pneumoniae. It was concluded thatC. pneumoniae is a common etiological agent for community-acquired pneumonia in our region, particularly in the elderly, and is characterized by a high rate of concomitant infections with other pulmonary pathogens. No specific clinical or radiological pattern was discerned that could distinguish betweenC. pneumoniae community-acquired pneumonia and non-C. pneumoniae community-acquired pneumonia.ZusammenfassungUnter 346 im Rahmen einer prospektiven Studie erfaßten Patienten mit ambulant erworbener Pneumonie fanden sich 62 Fälle (17,9%), bei denenChlamydia pneumoniae als der verantwortliche Erreger identifiziert wurde. Die Studie lief über einen Zeitraum von einem Jahr am Soroka Medical Center in Beer-Sheva, Israel. Die Diagnose basierte auf dem serologischen Nachweis von anti-C. pneumoniae Antikörpern mit der MIF-Technik. Bei 43 dieser Patienten fand sich mindestens noch ein zusätzlicher Erreger (69,4%). Bei 34 Patienten wurdeStreptococcus pneumoniae isoliert (54,8%). Patienten mit einerC. pneumoniae-Infektion waren signifikant älter als Patienten, bei denenC. pneumoniae nicht der Erreger war (p=0,03), diese Patienten hatten außerdem bei Einweisung einen höheren APACHE Score (p<0,05), häufiger positive Blutkulturen (p=0,02) und mußten länger stationär behandelt werden (p=0,022). Obwohl keine erregerspezifische Behandlung vorgenommen worden war, erholten sich 7 Patienten, die an einerC. pneumoniae Pneumonie erkrankt waren. Wir schließen aus den Daten, daßC. pneumoniae in unserer Region ein häufiger Pneumonieerreger ist, der vorwiegend ältere Personen befällt. Typischerweise besteht eine hohe Rate an Begleitinfektionen mit anderen Pneumonieerregern. Wir fanden kein spezifisches radiologisches Muster oder klinische Konstellationen, die eine Unterscheidung zwischenC. pneumoniae-Pneumonie und Pneumonien anderer Ätiologie ermöglichen würden.

Pseudomonal Infections in Patients with COPD

COPD is a common disease with increasing prevalence. The chronic course of the disease is characterized by acute exacerbations that cause significant worsening of symptoms. Bacterial infections play a dominant role in approximately half of the episodes of acute exacerbations of COPD. The importance of pseudomonal infection in patients with acute exacerbations of COPD stems from its relatively high prevalence in specific subgroups of these patients, and particularly its unique therapeutic ramifications. The colonization rate of Pseudomonas aeruginosa in patients with COPD in a stable condition is low.A review of a large number of clinical series of unselected outpatients with acute exacerbations of COPD revealed that P. aeruginosa was isolated from the patients’ sputum at an average rate of 4%. This rate increased significantly in COPD patients with advanced airflow obstruction, in whom the rate of sputum isolates of P. aeruginosa reached 8–13% of all episodes of acute exacerbations of COPD. However, the great majority of bacteria isolated in these patients were not P. aeruginosa, but the three classic bacteria Streptococcus pneumoniae, Hemophilus influenzae, and Moraxella catarrhalis. The subgroup of patients, with acute exacerbations of COPD, with the highest rate of P. aeruginosa infection, which approaches 18% of the episodes, is mechanically ventilated patients. However, even in this subgroup the great majority of bacteria isolated are the above-mentioned three classic pathogens.In light of these epidemiologic data and other important considerations, and in order to achieve optimal antibacterial coverage for the common infectious etiologies, empiric antibacterial therapy should be instituted as follows. Patients with acute exacerbations of COPD with advanced airflow obstruction (FEV1 <50% of predicted under stable conditions) should receive once daily oral therapy with one of the newer fluoroquinolones, i.e. levofloxacin, moxifloxacin, gatifloxacin, or gemifloxacin for 5–10 days. Patients with severe acute exacerbations of COPD who are receiving mechanical ventilation should receive amikacin in addition to one of the intravenous preparations of the newer fluoroquinolones or monotherapy with cefepime, a carbapenem or piperacillin/tazobactam. In both subgroups it is recommended that sputum cultures be performed before initiation of therapy so that the results can guide further therapy.

Seasonal variation in hospital admission for community-acquired pneumonia: A 5-year study

OBJECTIVES We conducted a retrospective analysis of computerized hospitalization and regional meteorological and geophysical data in a university hospital in southern Israel. The aim of the study was to determine and depict the seasonal variation in hospitalization for community-acquired pneumonia (CAP-H) and the factors affecting it, for all age groups combined and by age group, over a 5-year period. METHODS All cases of CAP-H over the period from January 1, 1990 to December 31, 1994 were studied by season of the year and age group. The rates of CAP-H for the four seasons were compared by t-tests. Mathematical models based on quasi-Fourier generalized linear models were developed and used to evaluate potential variables and their relative contributions to CAP-H. RESULTS A total of 4101 CAP-H were analysed in the study. Throughout the study period the prevalence of CAP-H was significantly higher in the winter and spring than in the summer and fall for all age groups combined and within each age group (P<0.00001). When CAP-H was compared between the winter and the spring, we found that in the 0-16 age group CAP-H was higher in the winter (P<.0.00001), in the 17-64 age group it was higher in the spring (P<0.002), and in the 65+ age group as well as for all age groups combined there were no significant differences between these two seasons. The most important factor explaining the variance in CAP-H in the 0-16 age group were direct and indirect effects of minimum daily temperature (31%), in the 17-64 age group direct and indirect effects of the difference between minimum and maximum daily temperatures (19%), and in the 65+ age group it was geophysical factors (13%). CONCLUSIONS There is a significant seasonal variation in CAP-H with higher rates for all age groups in the winter and spring. The extent to which the prevalence of CAP-H is dominant in the winter and spring seasons differs among the age groups, as does the principal variable explaining these differences. The most important factor is the direct and indirect effects of meteorological variables in the 0-16 and 17-64 age groups, and a geophysical one among the more elderly patients.