Bella Dvoskin

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.

Infection of Acanthamoeba polyphaga with Simkania negevensis and S. negevensis Survival within Amoebal Cysts

ABSTRACT Simkania negevensis, a novel microorganism belonging to the family Simkaniaceae in the orderChlamydiales, has an intracellular developmental cycle during which two morphological entities, elementary bodies (EB) and reticulate bodies (RB), are seen by electron microscopy. Rates of seropositivity to the organism are high in certain population groups, and S. negevensis has been associated with respiratory illness in humans. This study reports for the first time the ability ofS. negevensis to survive and grow insideAcanthamoeba polyphaga in addition to its known ability to grow in cell cultures of human or simian origin. Infectivity ofS. negevensis and growth in amoebae were monitored by immunoperoxidase assays. Long-term persistence and exponential growth of S. negevensis in amoebal trophozoites were demonstrated by infectivity assays and by electron microscopy. EB and dividing RB of S. negevensis were observed within inclusion bodies inside A. polyphaga. When S. negevensis-infected A. polyphaga amoebae were exposed to adverse conditions resulting in encystation of the amoebae, several possible outcomes were observed: cysts containing both normal amoebic cytoplasm and S. negevensis; cysts in whichS. negevensis cells were relegated to the space between cyst walls; and cysts containing S. negevensis, but apparently lacking amoebal cytoplasm. S. negevensiswithin dried amoebal cysts was capable of long-term survival. The possibility that amoebae may have a role in natural transmission ofS. negevensis needs to be investigated.

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.

Infections with the chlamydia-like microorganism Simkania negevensis, a possible emerging pathogen

Although evidence for the existence of numerous chlamydia-like microorganisms has been discovered in both environmental samples and clinical specimens, very few have been grown in vitro, and little is known of their pathogenic potential. Of all such organisms, Simkania negevensis is probably the most extensively studied. This review summarizes current knowledge about this intracellular bacterium, focusing especially on human infections.

Serological Evidence of Acute Infection with the Chlamydia-Like Microorganism Simkania negevensis (Z) in Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Abstract.The aims of this study were twofold: (i) to test for possible associations between serological evidence of acute Simkania negevensis (Sn) infection and acute exacerbation of chronic obstructive pulmonary disease and (ii) to examine the prevalence of past infections with Sn in patients with chronic obstructive pulmonary disease. In 120 patients (63%) there was serological evidence of past infection with Sn, which was not significantly different from the rate in a control population. In five hospitalizations serological evidence existed of acute infection with Sn around the time of the exacerbation of chronic obstructive pulmonary disease. In four of these cases, there was serological evidence of acute infection with at least one other respiratory pathogen. It is concluded that Sn can be associated serologically with exacerbation of chronic obstructive pulmonary disease, in most cases together with other respiratory pathogens. The implications of these findings should be investigated further.

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.

Detection of Simkania negevensis by culture, PCR, and serology in respiratory tract infection in Cornwall, UK

Respiratory tract infections are often treated empirically without investigation to detect the aetiological agent, which may be a virus or a bacterium, including atypical pathogens such as Chlamydophila pneumoniae or Mycoplasma pneumoniae. Recently, several types Chlamydia-like intracellular bacteria have been detected in environmental samples and clinical specimens. Little is known of their geographical distribution and potential pathogenicity. We describe the detection, by PCR and isolation in cell culture, of Simkania negevensis in nasopharyngeal aspirates of paediatric patients with bronchiolitis in Cornwall, UK. We also present serological evidence of exposure to the organism in 62% of adult patients and 46% of a sample of pregnant women. Empirical treatment of serious respiratory tract infection should consider the possible contribution of these organisms.

Evidence for the Presence of Simkania negevensis in Drinking Water and in Reclaimed Wastewater in Israel

ABSTRACT Simkania negevensis is a recently discovered chlamydia-like intracellular microorganism which has been associated with bronchiolitis in infants and with community-acquired pneumonia in adults; a high seroprevalence of antibodies to the microorganism has been found in various population groups. S. negevensis can be grown in various cell lines as well as in free-living amoebae such as Acanthamoeba polyphaga. In this study, evidence for the existence of Simkania or Simkania-like microorganisms in drinking water and in reclaimed wastewater is presented for the first time. Detection of the microorganism was made possible by the development of a specific and sensitive filter membrane immunoassay and was confirmed by PCR detection of microbial DNA in the water samples. The common presence of S. negevensis in water sources together with the high seroprevalence of antibodies to it and early age of acquisition of infection may implicate water as a source of infection. The possible significance of this finding for public health and for municipal water testing and treatment needs to be further examined.

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.