| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Guest Access | Sign In via User Name/Password
|
|
|
|||||||
Guest Access | Sign In via User Name/Password |
|||||||||
Dr. Wunderink is Director of Clinical Research, Methodist Le Bonheur Healthcare, and Dr. Waterer is Senior Lecturer in Respiratory Medicine, Department of Medicine, University of Western Australia, Royal Perth Hospital.
Correspondence to: Richard G. Wunderink, MD, FCCP, Methodist Le Bonheur Healthcare, 1265 Union Ave, 501 Crews Wing, Memphis, TN 38104-2499; e-mail: wunderiR{at}methodisthealth.org
Even with extensive diagnostic regimens, most studies
of community-acquired pneumonia (CAP) fail to determine the
etiology in 
50% of cases. In usual clinical practice, the
diagnostic rate is closer to 15%, which results in most patients with
CAP receiving an empiric antibiotic regimen rather than individualized
therapy. The choice of empiric antibiotic agents is often guided by
consensus guidelines.1
2
These guidelines are in turn
based on covering the majority of pathogens identified in published
findings from groups of patients with CAP.
Empiric therapy that does not cover the infecting pathogen is an
independent predictor of poor outcome,3
4
5
and patients
with subsequent changes in antibiotic therapy based on culture results
still have a significant mortality.6
7
The adverse
implications for inadequate empiric therapy make it imperative that the
antibiotic regimen chosen has as few "holes" as possible,
especially in patients with severe CAP, where the mortality is
20%. As the study by Chen and colleagues in this edition of
CHEST demonstrates (see page 1072), significant holes in
antibiotic coverage may result when the local etiology of CAP differs
from the etiology in "standard" populations (predominantly North
American and Western European) on which the guidelines are based. To
achieve the best outcome, physicians need to have knowledge of local
variations in the etiology of CAP, and they must be aware of which
pathogens may not be covered by standard empiric regimens, and the risk
factors for infection with these pathogens.
Deficiencies in empiric antibiotic coverage can result from either unexpected antibiotic resistance in the common pathogens or because unusual pathogens are the cause of CAP. The impact of antibiotic resistance is dependent on the empiric antibiotic regimen used. In the case of penicillin-resistant Streptococcus pneumoniae infection, the impact is relatively small because empiric regimens in areas with a high prevalence of penicillin resistance are designed to cover this eventuality. Conversely, while Staphylococcus aureus is not an unexpected pathogen, the presence of methicillin resistance in community-acquired infections is increasing8 and the inadequacy of usual empiric regimens may significantly impact outcome.4
The occurrence of etiologies other than the usual pathogens, S pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella spp, and respiratory viruses, increases the complexity of CAP management. It is reassuring that aggressive diagnostic procedures, such as percutaneous needle aspirates and preantibiotic bronchoscopy, or research protocols, such as polymerase chain reaction testing regularly find that the pneumococcus is the most common etiology for these otherwise undiagnosed cases. Convalescent serologic studies also consistently confirm that the usual "atypical" microorganisms cause another large percentage of cases, although the relative frequency of each varies depending on the geographic location of the study.
However, a disturbing percentage of patients with CAP, particularly those with severe CAP, are infected with pathogens not covered by the usual empiric antibiotic regimens. The more serious of this second tier of causative microorganisms are the Gram-negative bacilli. A study by Ruiz and coworkers9 found that Gram-negative bacilli (other than Haemophilus spp) caused 11% of CAP in patients requiring ICU admission. The mortality of severe Gram-negative CAP was 55.5%, the highest case fatality rate for any etiology.9 Gram-negative pathogens, particularly Klebsiella pneumoniae and Pseudomonas aeruginosa, are also frequently identified in patients presenting with CAP and shock,10 where the mortality is > 50%.
In this issue of CHEST, Chen and colleagues present a case series of severe CAP due to another Gram-negative bacillus, Acinetobacter baumannii. While usually considered a nosocomial pathogen, numerous cases of A baumannii CAP have been reported over many years, particularly in patients with severe CAP.10 11 One of the most helpful hints from the series reported by Chen et al is the geographic and temporal distribution of Acinetobacter CAP cases to areas and seasons of heat and humidity. The other helpful hint on diagnosis is that Acinetobacter CAP often has a presentation similar to the alcoholism, leukopenia, and pneumococcal bacteremia syndrome.11 12
Obviously, the greatest concern when unusual pathogens cause CAP is whether they are susceptible to the usual empiric antibiotic regimens. Although not as active as ciprofloxacin, empiric use of the newer quinolones for empiric therapy of CAP may provide some coverage of Pseudomonas, while the other common regimen of a nonpseudomonal cephalosporin and a macrolide would not. Acinetobacter CAP presents an even greater challenge because even antipseudomonal cephalosporins are infrequently effective. Carbapenems (imipenem and meropenem), seldom used but mentioned as an alternative by both American Thoracic Society and Infectious Disease Society of America guidelines, are the most reliable antibiotic agents for Acinetobacter pneumonia. However, Chen et al found that the addition of an aminoglycoside to a ß-lactam was associated with better outcome.
Unfortunately, outcomes analyses of CAP treatment have cast aminoglycoside use in a bad light. A large study14 of CAP treatment regimens suggested the inclusion of an aminoglycoside was associated with an increased risk of death. Rather than substandard empiric therapy, the association between mortality and aminoglycosides may be due to physicians correctly suspecting a Gram-negative pathogen with its attendant greater mortality. Combination therapy with a ß-lactam and an aminoglycoside has been demonstrated to lead to improved mortality in Klebsiella CAP,14 and aminoglycosides are routinely used in combination therapy for suspected pseudomonal infections.
Physicians want to select empiric antibiotic therapy that is likely to cover all likely pathogens, particularly in patients with severe CAP. How then should physicians select antibiotic regimens in patients with severe CAP in order to plug the occasional holes in standard empiric therapy? Indiscriminate use of a carbapenem or addition of an aminoglycoside to all patients with severe CAP is clearly not appropriate. However, the epidemiologic clues for unusual etiologies of CAP can justify selective use of these agents. Severe CAP occurring during hot, humid weather probably is an adequate indication for empiric carbapenem use for suspected Acinetobacter CAP, particularly if occurring in an active alcoholic or associated with neutropenia.
Most importantly, physicians need to be aware of the local differences in the etiology of CAP and the risk factors for pathogens likely to be resistant to standard empiric antibiotic regimens. When very broad-spectrum empiric therapy is selected to cover for drug-resistant pathogens, adequate blood and respiratory specimens must be collected to maximize the possibility of converting to specific therapy as soon as possible. Empiric therapy is indicated for infections in which the diagnostic yield is low or until diagnostic culture results are available. The success of empiric therapy in a majority of cases also does not justify laxity in diagnostic efforts in individual high-risk, high-yield cases.
References
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
