Levofloxacin Treatment Failure in a Patient with Fluoroquinolone‐Resistant Streptococcus pneumoniae Pneumonia

Abstract

The frequency of fluoroquinolone-resistant Streptococcus pneumoniae has increased as fluoroquinolone administration for treatment of respiratory tract infections has increased. Levofloxacin treatment failed in a patient who had pneumococcal pneumonia and had received three previous courses of levofloxacin therapy. Susceptibility testing revealed high-level resistance to levofloxacin (minimum inhibitory concentration [MIC] > 32 microg/ml), and cross-resistance to moxifloxacin (MIC 4 microg/ml), trovafloxacin (6 microg/ml), and gatifloxacin (12 microg/ml). Sequencing of the quinolone-resistance determining region revealed a mutation of serine-81 to phenylalanine (Ser81-->Phe) in the gyrA region of DNA gyrase and a Ser79-->Phe mutation in the parC region of topoisomerase IV The patient was treated successfully with intravenous ceftriaxone followed by oral cefprozil. Clinicians must be aware of local resistance patterns and the potential for fluoroquinolone treatment failures in patients with infections caused by S. pneumoniae.

Mutant Selection Window in Levofloxacin and Moxifloxacin Treatments of Experimental Pneumococcal Pneumonia in a Rabbit Model of Human Therapy

“…Recently, reports of failures to LVX treatment of pneumococcal diseases have been occurring (16,23,25,37,39,64,69,71). Some of these failures occurred in patients previously exposed to fluoroquinolones and/or when the pneumococcus exhibited an decreased susceptibility to fluoroquinolones, which was sometimes related to a preexisting parC mutation.…”

“…Recently, two major observations have emerged: first, failures of LVX treatment for pneumococcal pneumonia have been described in patients, most of whom were previously exposed to fluoroquinolones (16,24,37,39,64,69,71; N. Fishman, B. Suh, L. Weigel, B. Lorber, S. Gelone, A. Truant, T. Gootz, J. Christie, and P. Edelstein, Abstr.…”

Comparative Bacteriological Efficacy of Pharmacokinetically Enhanced Amoxicillin-Clavulanate against Streptococcus pneumoniae with Elevated Amoxicillin MICs and Haemophilus influenzae

“…As tissue concentrations were not measured in these studies, this postulation is impossible to either confirm or deny. In clinical studies, sporadic failures with levofloxacin have been documented against quinolone-resistant pneumococci, and failures against initially susceptible strains that developed quinolone resistance while on therapy have also been reported (7,8,19), although no changes in levofloxacin MICs were seen in this study.…”

Resistencias bacterianas y farmacodinámica como bases de la prescripción de antibióticos en infecciones respiratorias

“…A lo largo de los últimos años se han documentado bastantes fracasos confirmados bacteriológicamente con ciprofloxacino y más recientemente con levofloxacino 25,[49][50][51] . A diferencia de lo que ocurre con los betalactámicos, en los que las cepas resistentes son casi siempre el resultado de la adquisición de un gen de resistencia antes del inicio del tratamiento, en las fluoroquinolonas es frecuente que la resistencia se desarrolle durante la terapia 49 , lo cual explicaría la existencia de fracasos terapéuticos poco después de su comercialización en zonas con baja prevalencia de resistencias.…”