Bacterial complications of respiratory tract viral illness: a comprehensive evaluation.

BACKGROUND: Respiratory tract infection is one of the most common reasons for hospitalization among adults, and recent evidence suggests that many of these illnesses are associated with viruses. Although bacterial infection is known to complicate viral infections, the frequency and impact of mixed viral-bacterial infections has not been well studied. METHODS: Adults hospitalized with respiratory illness during 3 winters underwent comprehensive viral and bacterial testing. This assessment was augmented by measuring the serum level of procalcitonin (PCT) as a marker of bacterial infection. Mixed viral-bacterial infection was defined as a positive viral test result plus a positive bacterial assay result or a serum PCT level of ≥ 0.25 ng/mL on admission or day 2 of hospitalization. RESULTS: Of 842 hospitalizations (771 patients) evaluated, 348 (41%) had evidence of viral infection. A total of 212 hospitalizations (61%) involved patients with viral infection alone. Of the remaining 136 hospitalizations (39%) involving viral infection, results of bacterial tests were positive in 64 (18%), and PCT analysis identified bacterial infection in an additional 72 (21%). Subjects hospitalized with mixed viral-bacterial infections were older and more commonly received a diagnosis of pneumonia. Over 90% of hospitalizations in both groups involved subjects who received antibiotics. Notably, 4 of 10 deaths among subjects hospitalized with viral infection alone were secondary to complications of Clostridium difficile colitis. CONCLUSIONS: Bacterial coinfection is associated with approximately 40% of viral respiratory tract infections requiring hospitalization. Patients with positive results of viral tests should be carefully evaluated for concomitant bacterial infection. Early empirical antibiotic therapy for patients with an unstable condition is appropriate but is not without risk.

Factors associated with symptomatic rhinovirus infection in patients with COPD.

BACKGROUND: Human rhinoviruses (HRV) can be detected by RT-PCR in a large proportion of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) but can also be detected in COPD patients without symptoms. OBJECTIVES: The purpose of this study was to compare host, virologic and environmental factors associated with symptomatic and asymptomatic HRV infection. STUDY DESIGN: One hundred twenty-seven patients with COPD were evaluated every 2 months routinely and for all respiratory illnesses during a one year period. RT-PCR testing for HRV was performed on nasal and sputum samples. Amplification products were sequenced to assign species HRV-A, B or C. Clinical, virologic and environmental factors were compared for those infected with HRV compared to those without HRV infection as well as symptomatic HRV infection and asymptomatic HRV infection. RESULTS: HRVs were detected in 29 participants during 20 illnesses and 11 routine visits. HRV was detected in nasal samples from 15/102 (14.7%) illnesses compared to 2/685 (0.4%) routine visits (p<.0001). Sputum samples were also more frequently positive from illnesses than routine visits [14/72 (19.4%) vs. 16/310 (5.2%) p<.0001]. Contact with school age children was the only factor that was significantly associated with HRV infection and symptomatic HRV illness. Severity of underlying lung disease and virologic factors were not associated with symptomatic illness. CONCLUSIONS: Contact with school aged children is a risk factor for both infection and symptomatic HRV illness. Attention to good hand hygiene and avoidance of direct contact with ill children may help patients with COPD avoid HRV related illness.

Utility of serum procalcitonin values in patients with acute exacerbations of chronic obstructive pulmonary disease: a cautionary note.

BACKGROUND: Serum procalcitonin levels have been used as a biomarker of invasive bacterial infection and recently have been advocated to guide antibiotic therapy in patients with chronic obstructive pulmonary disease (COPD). However, rigorous studies correlating procalcitonin levels with microbiologic data are lacking. Acute exacerbations of COPD (AECOPD) have been linked to viral and bacterial infection as well as noninfectious causes. Therefore, we evaluated procalcitonin as a predictor of viral versus bacterial infection in patients hospitalized with AECOPD with and without evidence of pneumonia. METHODS: Adults hospitalized during the winter with symptoms consistent with AECOPD underwent extensive testing for viral, bacterial, and atypical pathogens. Serum procalcitonin levels were measured on day 1 (admission), day 2, and at one month. Clinical and laboratory features of subjects with viral and bacterial diagnoses were compared. RESULTS: In total, 224 subjects with COPD were admitted for 240 respiratory illnesses. Of these, 56 had pneumonia and 184 had AECOPD alone. A microbiologic diagnosis was made in 76 (56%) of 134 illnesses with reliable bacteriology (26 viral infection, 29 bacterial infection, and 21 mixed viral bacterial infection). Mean procalcitonin levels were significantly higher in patients with pneumonia compared with AECOPD. However, discrimination between viral and bacterial infection using a 0.25 ng/mL threshold for bacterial infection in patients with AECOPD was poor. CONCLUSION: Procalcitonin is useful in COPD patients for alerting clinicians to invasive bacterial infections such as pneumonia but it does not distinguish bacterial from viral and noninfectious causes of AECOPD.

Humoral immunity to human metapneumovirus infection in adults.

Human metapneumovirus (hMPV) is a significant cause of respiratory illness in children and adults. Presently, there are no human data regarding the role of antibody for protection against hMPV illness. Therefore, we measured serum and nasal antibody titers against hMPV by EIA and neutralization assay at baseline in hMPV infected adults compared with subjects who remained uninfected. Antibody titers were also compared in patients with mild and severe illness. Mean serum binding and neutralizing antibody titers of hMPV infected subjects were significantly lower compared to uninfected subjects. Seventy-one percent of subjects with titers 10.5, p=0.003. There was no difference in the mean acute antibody titers for patients with mild compared to severe illness. Serum antibody may play a role in protection from hMPV infection supporting the development of an hMPV vaccine that stimulates humoral immunity.

Detection of respiratory syncytial virus in adults with chronic obstructive pulmonary disease.

RATIONALE: Recently, respiratory syncytial virus (RSV) RNA has been identified by reverse transcriptase-polymerase chain reaction (RT-PCR) from a high percentage of patients with stable chronic obstructive pulmonary disease (COPD). These data raise the possibility of persistent low-grade infection in this population, which could have implications in COPD pathogenesis. OBJECTIVES: RSV persistence was investigated by testing respiratory secretions from subjects with COPD during illness and at regular intervals over 1 yr. METHODS: Nasal and sputum samples from subjects with COPD were tested by one-tube nested RT-PCR for RSV every 2 mo and during respiratory illnesses for 1 yr. Subjects positive for RSV were evaluated weekly until negative in two consecutive samples. Nasal secretions and serum were tested for RSV antibody. A rise of fourfold or greater was defined as evidence of RSV infection. RESULTS: A total of 112 patients were enrolled and the illnesses of 92 patients were evaluated. RSV was detected by RT-PCR in 6/92 (6.5%) illness nasal samples versus 0/685 routine nasal samples and in 5/69 (7.2%) illness sputum samples versus 3 /315 (0.9%) routine. Four additional RSV infections were identified by serum antibody responses. Of the RSV infections 86% were associated with serum or nasal antibody responses and 73% had symptoms of acute respiratory illness. CONCLUSIONS: Most RSV infections in patients with COPD are associated with symptomatic respiratory illnesses and measurable immune responses. Our data do not support the concept of RSV persistence in this population.