title: Failure of levofloxacin treatment in community-acquired pneumococcal pneumonia.
abstract: BACKGROUND
  Streptococcus pneumoniae is the leading cause of community-acquired pneumonia (CAP). High global incidence of macrolide and penicillin resistance has been reported, whereas fluoroquinolone resistance is uncommon. Current guidelines for suspected CAP in patients with co-morbidity factors and recent antibiotic therapy recommend initial empiric therapy using one fluoroquinolone or one macrolide associated to other drugs (amoxicillin, amoxicillin/clavulanate, broad-spectrum cephalosporins). Resistance to fluoroquinolones is determined by efflux mechanisms and/or mutations in the parC and parE genes coding for topoisomerase IV and/or gyrA and gyrB genes coding for DNA gyrase. No clinical cases due to fluoroquinolone-resistant S. pneumoniae strains have been yet reported from Italy.
  
  
  METHODS
  A 72-year-old patient with long history of chronic obstructive pulmonary disease and multiple fluoroquinolone treatments for recurrent lower respiratory tract infections developed fever, increased sputum production, and dyspnea. He was treated with oral levofloxacin (500 mg bid). Three days later, because of acute respiratory insufficiency, the patient was hospitalized. Levofloxacin treatment was supplemented with piperacillin/tazobactam. Microbiological tests detected a S. pneumoniae strain intermediate to penicillin (MIC, 1 mg/L) and resistant to macrolides (MIC >256 mg/L) and fluoroquinolones (MIC >32 mg/L). Point mutations were detected in gyrA (Ser81-Phe), parE (Ile460-Val), and parC gene (Ser79-Phe; Lys137-Asn). Complete clinical response followed treatment with piperacillin/tazobactam.
  
  
  CONCLUSIONS
  This is the first Italian case of community-acquired pneumonia due to a fluoroquinolone-resistant S. pneumoniae isolate where treatment failure of levofloxacin was documented. Molecular analysis showed a group of mutations that have not yet been reported from Italy and has been detected only twice in Europe. Treatment with piperacillin/tazobactam appears an effective means to inhibit fluoroquinolone-resistant strains of S. pneumoniae causing community-acquired pneumonia in seriously ill patients.
authors.affiliation: Laboratory of Microbiology and Virology, University of Insubria and Ospedale di Circolo e Fondazione Macchi, Varese, Italy. aendimiani@tin.it
authors.forename: Andrea
authors.initials: A
authors.lastname: Endimiani
authors.forename: Gioconda
authors.initials: G
authors.lastname: Brigante
authors.forename: Alessia A
authors.initials: AA
authors.lastname: Bettaccini
authors.forename: Francesco
authors.initials: F
authors.lastname: Luzzaro
authors.forename: Paolo
authors.initials: P
authors.lastname: Grossi
authors.forename: Antonio Q
authors.initials: AQ
authors.lastname: Toniolo
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins / Q000235:genetics; D017714:Community-Acquired Infections / Q000188:drug therapy*; D004250:DNA Topoisomerases, Type II / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D064704:Levofloxacin; D015242:Ofloxacin / Q000494:pharmacology* / Q000627:therapeutic use*; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D010878:Piperacillin / Q000627:therapeutic use; D000077725:Piperacillin, Tazobactam Drug Combination; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy*; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D013301:Streptolysins / Q000235:genetics; D017211:Treatment Failure
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae; D000077725:Piperacillin, Tazobactam Drug Combination; D064704:Levofloxacin; D010397:Penicillanic Acid; D015242:Ofloxacin; D004250:DNA Topoisomerases, Type II; D010878:Piperacillin