Ida Boldur

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.

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.

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.

Chlamydia pneumoniae Infection in Acute Exacerbations of Chronic Obstructive Pulmonary Disease: Analysis of 250 Hospitalizations

Abstract. Two hundred fifty hospitalizations were included in a serologically based prospective study to assess the role of Chlamydia pneumoniae in episodes of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and the percentage of COPD patients chronically infected with this pathogen. Chlamydia pneumoniae-specific IgG, IgA and IgM antibody titers were determined using a commercial kit with the microimmunofluorescence method. A significantly higher geometric mean titer in the COPD patients compared to the control group was found for IgG (P<0.00001) and IgA (P<0.000001). The serological criterion for chronic Chlamydia pneumoniae infection (IgG ≥128 concomitant with IgA ≥64) was positive in 73 (33.3%) COPD patients compared with 7 (7%) controls (P=0.000001). No difference was found in any serological parameter when the study population was divided by severity of COPD. When the serological profiles were compared between the first and second of 31 pairs of hospitalizations, 7 of the 62 (11.3%) hospitalizations showed evidence of acute infection with Chlamydia pneumoniae around one of the episodes of AECOPD. It is concluded that compared with the control group, the COPD patients had a significantly higher prevalence of chronic Chlamydia pneumoniae infection. In the COPD group, there was no correlation between the severity of the disease and the rate of chronic Chlamydia pneumoniae infection. In a substantial percentage of AECOPD cases, there is serological evidence of acute Chlamydia pneumoniae infection around the time of the exacerbation. The clinical and pathophysiologic implications of these findings should be clarified by further studies.

Etiology of respiratory tract infection in adults in a general practice setting.

Abstract A prospective study was conducted over a 3-month winter period in three general practice clinics in an urban population in southern Israel to identify the etiological agents of respiratory tract infections (RTI) in adults. RTI was defined as an acute febrile illness with cough, coryza, sore throat or hoarseness. Serum samples were taken from all patients in both the acute and convalescent phases of their illness. Tests were conducted for detection of 17 microorganisms known to cause RTI, including serological tests for 16 known pathogens. An etiological diagnosis was established in 80 (66%) of the 122 patients who participated in the study. The distribution of the etiological agents was as follows: influenza B virus in 27 (22%) patients, Chlamydia pneumoniae in 22 (18%), Legionella spp. in 15 (12%), Mycoplasma pneumoniae in 13 (11%), influenza A virus in 11 (9%), Bordetella pertussis in 9 (7%), adenovirus in 4, Epstein Barr virus in 4, Haemophilus influenzae in 3, β-hemolytic streptococci in 3, Streptococcus pneumoniae in 2, respiratory syncytial virus in 2, parainfluenza 1 virus in 2 and parainfluenza 2 virus in 1. No patients were found to be infected with Coxiella burnetii, Moraxella catarrhalis or parainfluenza 3 virus. More than one pathogen was identified in 27 (34%) patients in whom an etiological diagnosis was established. It is concluded that RTI is caused by a broad spectrum of etiological agents, a considerable number of patients having evidence of infection with more than one pathogen. The therapeutic significance of these findings should be elucidated in further studies.

A comparative study of the etiology of adult upper and lower respiratory tract infections in the community

Abstract Lower respiratory tract infection and upper respiratory tract infection (URTI) are very common, but the etiology is not diagnosed in routine practice. The objective of this study was to determine and compare the frequency distribution of the various infectious etiologies for these diseases. One hundred seventy five adults in the community with febrile LRTI and 75 with febrile URTI were included in a purely serologically based prospective study. Paired sera were obtained for each of the patients and were tested by EIA or immunofluorescence methods to identify 14 different pathogens. Only a significant change in antibody titers between the paired sera was considered diagnostic. At least one infectious etiology was identified in 167 patients (67%). In the LRTI group, infection with at least one of 7 respiratory viruses was found in 88 patients (50%). One of the atypical pathogens was found in 40 patients (23%), of these Legionella spp. in 19 (11%) and Mycoplasma pneumoniae in 18 (10%). A bacterial etiology was found in 19 patients (11%), of these Streptococcus pneumoniae in 8 (5%) and β-hemolytic streptococci group A in 5 (3%). The frequency distribution of etiologies in the URTI group was not significantly different from the LRTI group, except for M. pneumoniae that was identified in only one patient with URTI (p = 0.015). More than one etiologic agent was found in 42 (17%) of the patients. LRTI is caused by a broad spectrum of etiologies, with respiratory viruses predominating and a moderate, but significant, prevalence of atypical pathogens. The frequency distribution of etiologies for URTI is similar to LRTI. In a significant proportion of patients with URTI and LRTI there is serologic evidence of infection with more than one pathogen. The justification and benefit of distinguishing between URTI and LRTI in routine clinical work is doubtful. When a decision is reached to treat RTI patients with an antibiotic, it is logical to use a macrolide or tetracycline.

Colonization rate of bacteria in the throat of healthy infants

OBJECTIVE the human throat is a major ecological site for various bacteria that can reach neighbouring sterile sites and cause mild infections or invasive diseases. The aim of this study was to investigate the carriage rate of several potential pathogens in the throat of healthy children under the age of 2 years. METHODS cultures were taken from the tonsils of 1000 healthy infants aged 1-24 months attending well-baby clinics, who had not received antibiotic therapy during the preceding 14 days. RESULTS one hundred and ninety-eight (19.8%) cultures were positive. Thirteen (1.3%) cultures were positive for beta-haemolytic Streptococcus group A, 23 (2.3%) for Streptococcus pneumoniae. In 28 (2.8%) and 24 (2.4%) cultures, respectively, Haemophilus influenzae Type b and non-typeable Haemophilus influenzae were recovered. The commonest bacterium found was Staphylococcus aureus (99 positive cultures). Eleven children carried two species of bacteria and from one 6-month-old child three species were isolated concurrently. CONCLUSIONS it is concluded that children younger than 2 years of age can be carriers of several types of pathogenic bacteria. In contrast to many other studies, in this study beta-haemolytic Streptococcus group A was isolated from the tonsils of children younger than 1 year of age.

Transferable resistance factors with mutator effect in Salmonella typhi

Abstract Strains of Salmonella typhi with different combinations of drug resistance were isolated from samples of feces from one patient. An analysis showed resistance to be caused by two transferable resistance factors, one carrying resistance to chloramphenicol (Cm) and dihydrostreptomycin (Sm), the other to tetracycline (Tc) alone, or to Tc and Sm. Cultures of S. typhi, S. typhimurium and Escherichia coli infected with these resistance factors were genetically unstable, showing high mutability to increased levels of resistance. The high resistance level of the mutants was transferred by conjugation. Plasmid elimination resulted in the loss of this resistance as well as of the high mutability. Results obtained with cultures infected simultaneously with two plasmids indicated that recombination between the Sm loci is possible. The investigation shows that mutations occur on the plasmids, and not as a consequence of interference with the bacterial nucleus.

Serious Consequences to the Use of Cephalosporins as the First Line of Antimicrobial Therapy Administered in Hemodialysis Units

Background: The dramatic spread of vancomycin-resistant enterococci (VRE) among hemodialysis (HD) patients led to the replacement of vancomycin with cephalosporins as part of the primary empiric therapy for bacterial infections in HD units. The aim of the study was to examine the effects of this new regimen on the colonization rate of resistant bacteria among HD patients. Methods: Rectal swabs were taken from 105 HD patients and 91 control hospitalized patients. Groups were matched for age, sex, nursing home residency and background diseases. Enterococci were tested for vancomycin resistance, Staphylococcus aureus isolates were tested for methicillin resistance (MRSA), and Enterobacteriaceae were tested for extended-spectrum β-lactamase (ESBL) activity. Results: In the HD group 1 VRE, 1 MRSA and 9 ESBL-producing organisms were isolated compared to 1 MRSA and 1 ESBL organism in the control group (p = 0.018 for ESBL). In the year prior to the study, the use of cephalosporins had been enhanced in the HD group compared to the control group (p < 0.001), and in the HD ESBL-positive patients compared to the HD ESBL-negative ones (p = 0.007). The overall use of antibiotics in the control group was the same as in the HD group. In a subanalysis of the HD group alone, the ESBL carriers were older, sicker, used more antibiotics, were hospitalized frequently and had a higher mortality rate, compared to noncarriers. Conclusions: The use of cephalosporins as first-line therapy in HD patients in central Israel reduced the prevalence of VRE colonization but may have contributed to the emergence of ESBL-producing organisms through induction of selection pressure. This may lead to serious complications in the management of these patients.

Infectious aetiologies in elderly patients hospitalised with non‐pneumonic lower respiratory tract infection

Abstract Objective: to identify the infectious aetiologies of non‐pneumonic lower respiratory tract infections in hospitalised elderly patients, and to characterise the patients in terms of demographic, clinical and therapeutic variables. Design: a prospective, non‐interventional, purely serologically based diagnostic study. Setting: a tertiary university hospital in southern Israel. Subjects: 133 elderly patients hospitalised for non‐pneumonic lower respiratory tract infections. Methods: paired sera were obtained for each of the hospitalisations and were tested using immunofluorescence or enzyme immunoassay methods to identify 13 different pathogens. Only significant changes in antibody titers or levels between the paired sera were considered diagnostic. Results: at least one infectious aetiology was identified in 77 patients (58%). At least one of seven viral aetiologies was identified in 52 patients (39%). A bacterial aetiology was identified in 27 patients (20%) including Streptococcus pneumoniae in 24 (18%). An atypical bacterium was found in 27 patients (20%) including Mycoplasma pneumoniae in 15 (11%) and Legionella spp. in nine (7%). More than one aetiology was found in 23 patients (17%). One hundred and twenty nine patients (96%) suffered from serious chronic co‐morbidity. One hundred and twenty one patients received antibiotics during their hospitalisation, 106 (80%) with a beta‐lactam and 42 (31%) with another antibiotic. Conclusions: non‐pneumonic lower respiratory tract infection is caused in hospitalised elderly patients by a broad spectrum of aetiological agents, primarily respiratory viruses with a significant, though lesser, prevalence of classical and atypical bacteria. Despite this distribution of aetiologies, most patients are treated with beta‐lactam antibiotics. The indication for antibiotic therapy in these patients and the choice of antibiotic preparation should be addressed in further studies.