MONTREAL — Respiratory fluoroquinolones for the treatment of community-acquired pneumonia should generally be restricted to hospitalized patients to minimize the development of resistance to the drugs among respiratory pathogens as well as colonization by other pathogens, said Thomas M. File Jr., M.D.
“Outpatient studies have shown that many [community-acquired pneumonia] patients who are given quinolones could have been given other agents as preferred first-line therapy, and investigators have identified incorrect dosing and duration patterns that could lead to the development of antibiotic resistance to quinolones,” Dr. File said at an international conference on community-acquired pneumonia.
Outpatient fluoroquinolone therapy should be considered only for patients at increased risk for drug-resistant Streptococcus pneumoniae, including those with comorbid conditions such as diabetes, chronic inflammatory lung disease, liver or renal insufficiency, malignancy, or congestive heart failure, and for patients who have been treated recently with antibacterial agents, said Dr. File, chief of the infectious disease service with Summa Health System in Akron, Ohio.
Since their introduction in the mid-1980s, fluoroquinolones have gained popularity because of their broad-spectrum coverage and high serum levels attained with oral administration—as well as increasing antibiotic resistance among pathogens. The approved agents, including gatifloxacin, gemifloxacin, levofloxacin, and moxifloxacin, are especially valuable for treating lower respiratory tract infections, given the growing prevalence of multiresistant pneumococci, Dr. File noted at the conference, sponsored by the International Society of Chemotherapy.
“The respiratory fluoroquinolones make excellent choices for therapy of community-acquired pneumonia because of their intrinsic activity against the key pathogens, including drug-resistant S. pneumoniae and the atypical organisms, and because of their excellent bioavailability and ability to penetrate well into pulmonary sites of infection,” he added. Another advantage is that the serum half-life is longer than that of other agents, including ciprofloxacin, allowing for once-daily dosing.
Numerous randomized trials have favored fluoroquinolones over standard therapy in terms of efficacy, and several have suggested that initial treatment with the respiratory fluoroquinolones can lead to a rapid clinical response, thus justifying shorter-course therapy for many patients and minimizing the possibility for noncompliance, Dr. File said.
For previously healthy outpatients with community-acquired pneumonia who have not received antimicrobial drugs within the prior 3 months, updated recommendations for empiric antimicrobial therapy suggest treatment with an extended-spectrum macrolide or doxycycline. For patients with comorbidities or who have received recent antimicrobial therapy, therapeutic options include a respiratory fluoroquinolone, a ketolide alone in the absence of enteric gram-negative bacteria, or a combination of a β-lactam plus a macrolide, Dr. File said.
“Another possible option for outpatients with modifying factors is the use of parenteral intramuscular or intravenous ceftriaxone plus an oral macrolide or doxycycline,” he noted.
For inpatient therapy in the general hospital ward, recommended initial therapy includes monotherapy with one of the respiratory fluoroquinolones or a β-lactam plus a macrolide or doxycycline.
“In some patients who don't have severe disease and have no risk factors for drug resistant S. pneumoniae or gram-negative pathogens, parenteral azithromycin monotherapy may be considered,” Dr. File said.
Initial treatment for patients in the intensive care unit “who are more likely to be very ill and to have multiple risk factors for more resistant pathogens” should be more aggressive, covering for both atypical organisms and traditional bacterial pathogens. Combination therapy with a potent antipneumococcal β-lactam and an advanced macrolide or a respiratory fluoroquinolone is recommended when Pseudomonas infection is not a consideration, he noted.
“The role of the respiratory fluoroquinolones for severe community-acquired pneumonia patients in the intensive care unit has not been established. Thus, fluoroquinolone monotherapy is not recommended in these patients,” Dr. File added.
In the presence of risk factors for Pseudomonas infection, as with severe structural lung diseases, “therapy should include drugs that are effective against pneumococcus, Pseudomonas, and Legionella,” he said.
Such therapies include an antipneumococcal, antipseudomonal β-lactam plus ciprofloxacin or levofloxacin; an antipneumococcal, antipseudomonal β-lactam plus an aminoglycoside and intravenous macrolide or intravenous macrolide or intravenous antipneumococcal quinolone; or, for patients with penicillin allergy, aztreonam plus levofloxacin or aztreonam plus moxifloxacin or gatifloxacin, with or without aminoglycoside.