A disease model descriptive of progression between chronic obstructive pulmonary disease exacerbations and community-acquired pneumonia: roles for underlying lung disease and the pharmacokinetics/pharmacodynamics of the antibiotic.

A disease model descriptive of progression between chronic obstructive pulmonary disease exacerbations and community-acquired pneumonia: roles for underlying lung disease and the pharmacokinetics/pharmacodynamics of the antibiotic.

File Thomas M Jr; Monte Scott V; Schentag Jerome J; Paladino Joseph A; Klugman Keith P; Lavin Bruce; Yu Victor L; Singer Mendel E; Adelman Martin H

International journal of antimicrobial agents

2009

2009-01

Patients with chronic obstructive pulmonary disease (COPD) may progress to community-acquired pneumonia (CAP), but there has been no formal study of the factors responsible. We studied the influence of severity of underlying lung disease, pathogen characteristics and the ratio of the area under the concentration-time curve from 0-24h to minimum inhibitory concentration (AUC24/MIC), i.e. the area under the inhibitory curve (AUIC), during the progression from acute exacerbation of chronic bronchitis (AECB) in COPD to CAP. The model parameters were derived from a multinational database of 3885 patients with AECB or CAP (April 1996 to July 2006). Patients with underlying COPD were evaluated in two separate analyses: infection progression between COPD and CAP within Global Initiative for Chronic Obstructive Lung Disease (GOLD)-like grouping (GLG); and distribution of pathogen by GLG, CAP and AECB. Secondary analyses examined the impact of target AUIC attainment on progression to CAP for Streptococcus pneumoniae. The relative impact of GLG and AUIC were modelled in multivariate logistic regression for S. pneumoniae. Progression to CAP linked directly with GLG I/II, III and IV (18.3%, 31.7% and 48.9%, respectively; P \textless 0.001). Progression to CAP was strongly associated with S. pneumoniae (57.3%), whilst other pathogens were predominant in AECB that did not progress to CAP (61.7%) (P = 0.002). AUIC \textgreater or = 100 was associated with AECB (65.1%) and AUIC \textless 100 with CAP (91.7%) (P \textless 0.001). In conclusion, the frequency of progression to CAP increases directly with GLG. For S. pneumoniae, achieving an AUIC \textgreater or =100 can attenuate progression, regardless of GLG. Thus, AUIC \textgreater or = 100 appears to be a viable antibiotic selection strategy to protect patients with S. pneumoniae from developing CAP.

*Anti-Bacterial Agents/pharmacokinetics/therapeutic use; *Community-Acquired Infections/drug therapy/microbiology/physiopathology/prevention & control; *Models; *Pneumonia; Aged; Area Under Curve; Bacterial/drug therapy/microbiology/physiopathology/prevention & control; Biological; Bronchitis; Chronic Obstructive/drug therapy/microbiology/*physiopathology; Chronic/drug therapy/microbiology/physiopathology; Disease Progression; Female; Humans; Lung Diseases/complications/drug therapy/microbiology; Lung/microbiology; Male; Microbial Sensitivity Tests; Middle Aged; Pneumococcal/drug therapy/microbiology/physiopathology/prevention & control; Pneumonia; Pulmonary Disease; Severity of Illness Index; Streptococcus pneumoniae/*drug effects

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