Antimicrobial susceptibility of Streptococcus pneumoniae isolates from vaccinated and non-vaccinated patients with a clinically confirmed diagnosis of community-acquired pneumonia in Belgium

Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
International journal of antimicrobial agents (Impact Factor: 4.26). 03/2012; 39(3):208-16. DOI: 10.1016/j.ijantimicag.2011.11.011
Source: PubMed

ABSTRACT We assessed the in vitro susceptibility of Streptococcus pneumoniae isolates from patients with confirmed community-acquired pneumonia (CAP) to β-lactams, macrolides and fluoroquinolones and the association of non-susceptibility and resistance with serotypes/serogroups (STs/SGs), patient's risk factors and vaccination status. Samples (blood or lower respiratory tract) were obtained in 2007-2009 from 249 patients (from seven hospitals in Belgium) with a clinical and radiological diagnosis of CAP [median age 61 years (11.6% aged <5 years); 85% without previous antibiotic therapy; 86% adults with level II Niederman's severity score]. MIC determination (EUCAST breakpoints) showed for: (i) amoxicillin, 6% non-susceptible; cefuroxime (oral), 6.8% resistant; (ii) macrolides: 24.9% erythromycin-resistant [93.5% erm(B)-positive] but 98.4% telithromycin-susceptible; and (iii) levofloxacin and moxifloxacin, all susceptible. Amongst SGs: ST14, all resistant to macrolides and most intermediate to β-lactams; SG19 (>94% ST19A), 73.5% resistant to macrolides and 18-21% intermediate to β-lactams; and SG6, 33% resistant to clarithromycin. Apparent vaccine failures: 3/17 for 7-valent vaccine (children; ST6B, 23F); 16/29 for 23-valent vaccine (adults ST3, 7F, 12F, 14, 19A, 22F, 23F, 33F). Isolates from nursing home residents, hospitalised patients and patients with non-respiratory co-morbidities showed increased MICs for amoxicillin, all β-lactams, and β-lactams and macrolides, respectively. Regarding antibiotic susceptibilities: (i) amoxicillin is still useful for empirical therapy but with a high daily dose; (ii) cefuroxime axetil and macrolides (but not telithromycin) are inappropriate for empirical therapy; and (iii) moxifloxacin and levofloxacin are the next 'best empirical choice' (no resistant isolates) but levofloxacin will require 500 mg twice-daily dosing for effective coverage.

  • [Show abstract] [Hide abstract]
    ABSTRACT: This study evaluated the pharmacokinetics of intravenous moxifloxacin 400mg once and levofloxacin 500mg twice daily in patients with lower respiratory tract infections (LRTIs) and assessed their pharmacodynamic adequacy against common respiratory pathogens. Eighteen patients with LRTIs hospitalised in general wards were included. Serial blood samples were obtained at steady state and concentrations were determined using HPLC. Pharmacokinetic variables were estimated by a two-compartment model. The characteristic pharmacodynamic parameter for fluoroquinolones (AUC0-24/MIC) was calculated. Peak and trough concentrations were, respectively, 4.81±1.03 and 0.59±1.13mg/L for moxifloxacin and 6.42±1.08 and 0.79±0.39mg/L for levofloxacin. Pharmacokinetic data for moxifloxacin and levofloxacin, respectively, were: CL, 10.27±1.24 and 22.66±6.62L/h; t1/2, 13.43±5.12 and 6.75±1.34h; Vss, 163.03±53.88 and 170.73±39.59L; and AUC0-24, 39.38±5.28 and 47.06±14.09mg·h/L. The pharmacodynamic target was attained in all patients by both antibiotics against the majority of respiratory pathogens. Moxifloxacin proved to be pharmacodynamically efficacious against Gram-positive bacteria with MICs≤0.79mg/L and Gram-negative bacteria with MICs≤0.32mg/L. These MIC thresholds for levofloxacin were 1.1mg/L and 0.38mg/L, respectively. Moxifloxacin and high-dose levofloxacin show a favourable pharmacokinetic profile in plasma of patients with severe LRTIs, without significant interpatient variability. They ensure optimal pharmacodynamic exposure against the majority of microbes involved in these infections. However, the predicted efficacy against Gram-negative bacteria with MICs≥0.5mg/L appears to be low.
    International journal of antimicrobial agents 07/2013; 42(3). DOI:10.1016/j.ijantimicag.2013.04.028 · 4.26 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Increasing levels of paediatric community-acquired pneumonia (CAP), caused by drug-resistant bacteria and antimicrobial resistance, vary with age and countries and, in some cases, serotypes. When empirical first-line treatment administration fails, paediatricians should consider second-line treatments based on the prevalence of local resistance. A more judicious use of antimicrobial agents is also required. Knowledge of local epidemiology and an appropriate use of antimicrobial drugs are necessary to treat CAP in this era of antimicrobial resistance.
    Acta paediatrica (Oslo, Norway: 1992). Supplement 12/2013; 102(465):25-33. DOI:10.1111/apa.12503
  • [Show abstract] [Hide abstract]
    ABSTRACT: The correlation between Streptococcus pneumoniae serotypes, biofilm production, antibiotic susceptibility and drug efflux in isolates from patients suffering from acute exacerbations of chronic bronchitis (AECB) remains largely unexplored. Using 101 isolates collected from AECB patients for whom partial (n = 51) or full (n = 50) medical details were available, we determined serotypes (ST)/serogroups (SG) (Quellung reaction), antibiotic susceptibility patterns [MIC (microdilution) using EUCAST and CLSI criteria] and ability to produce biofilm in vitro (10-day model; crystal violet staining). The majority of patients were 55–75 years old and <5% were vaccinated against S. pneumoniae. Moreover, 54% showed high severity scores (GOLD 3–4), and comorbidities were frequent including hypertension (60%), cancer (24%) and diabetes (20%). Alcohol and/or tobacco dependence was >30%. Isolates of SG6-11-15-23, known for large biofilm production and causing chronic infections, were the most prevalent (>15% each), but other isolates also produced biofilm (SG9-18-22-27 and ST8-20 being most productive), except SG7, SG29 and ST5 (<2% of isolates each). Resistance (EUCAST breakpoints) was 8–13% for amoxicillin and cefuroxime, 35–39% for macrolides, 2–8% for fluoroquinolones and 2% for telithromycin. ST19A isolates showed resistance to all antibiotics, ST14 to all except moxifloxacin, and SG9 and SG19 to all except telithromycin, moxifloxacin and ceftriaxone (SG19 only). Solithromycin and telithromycin MICs were similar. No correlation was observed between biofilm production and MIC or efflux (macrolides, fluoroquinolones). Streptococcus pneumoniae serotyping may improve AECB treatment by avoiding antibiotics with predictable low activity, but it is not predictive of biofilm production.
    International Journal of Antimicrobial Agents 09/2014; 44(3). DOI:10.1016/j.ijantimicag.2014.05.016 · 4.26 Impact Factor