title: A Monte Carlo pharmacokinetic/pharmacodynamic simulation to evaluate the efficacy of minocycline, tigecycline, moxifloxacin, and levofloxacin in the treatment of hospital-acquired pneumonia caused by Stenotrophomonas maltophilia.
abstract: BACKGROUND
  Stenotrophomonas maltophilia has emerged as an important opportunistic pathogen in recent years. Increasing antimicrobial resistance and other contraindications have greatly compromised trimethoprim/sulfamethoxazole (SXT) as the first-line therapeutic option. The objective of this study was to explore other options for treating hospital-acquired pneumonia (HAP) caused by S. maltophilia.
  
  
  METHODS
  A total of 102 strains of S. maltophilia were isolated from sputum and bronchoalveolar lavage (BAL) specimens of patients with HAP in our institution. The minimum inhibitory concentration (MIC) values of minocycline, tigecycline, moxifloxacin, and levofloxacin were determined by the agar dilution method. Based on the MICs and the population pharmacokinetic parameters of the investigated antimicrobials, a Monte Carlo simulation was performed to simulate the pharmacokinetic/pharmacodynamic (PK/PD) indices of different regimens. The probability of target attainment (PTA) was estimated at each MIC value and the cumulative fraction of response (CFR) was calculated to evaluate the efficacy of these regimens.
  
  
  RESULTS
  The susceptibility rates to minocycline, tigecycline, moxifloxacin, and levofloxacin were 96.1%, 80.4%, 74.5%, and 69.6%, respectively. The estimated CFRs were 96.2% for minocycline 100 mg twice daily; 50.8%/67.1%/75.4% for tigecycline 50/75/100 mg twice daily; 34.3%/48.0%/56.6% for levofloxacin 500/750/1000 mg once daily; and 45.7% for moxifloxacin 400 mg once daily.
  
  
  CONCLUSIONS
  The simulation results suggest that minocycline may be a proper choice for treatment of HAP caused by S. maltophilia, while tigecycline, moxifloxacin, and levofloxacin may not be optimal as monotherapy.
authors.affiliation: a From the Department of Respiratory Diseases , Chinese People's Liberation Army General Hospital , Beijing , China.
authors.forename: Chuanqi
authors.initials: C
authors.lastname: Wei
authors.affiliation: a From the Department of Respiratory Diseases , Chinese People's Liberation Army General Hospital , Beijing , China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Ni
authors.affiliation: a From the Department of Respiratory Diseases , Chinese People's Liberation Army General Hospital , Beijing , China.
authors.forename: Xuejiu
authors.initials: X
authors.lastname: Cai
authors.affiliation: a From the Department of Respiratory Diseases , Chinese People's Liberation Army General Hospital , Beijing , China.
authors.forename: Junchang
authors.initials: J
authors.lastname: Cui
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D003428:Cross Infection / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D024841:Fluoroquinolones / Q000493:pharmacokinetics / Q000494:pharmacology; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D064704:Levofloxacin / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D009010:Monte Carlo Method; D000077266:Moxifloxacin; D011014:Pneumonia / Q000188:drug therapy* / Q000382:microbiology; D013183:Sputum / Q000382:microbiology; D020615:Stenotrophomonas maltophilia / Q000187:drug effects* / Q000302:isolation & purification / Q000472:pathogenicity*; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D064704:Levofloxacin; D000078304:Tigecycline; D008911:Minocycline; D000077266:Moxifloxacin
keywords: Hospital-acquired pneumonia; Monte Carlo simulation; Stenotrophomonas maltophilia