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: 4.3). 03/2012; 39(3):208-16. DOI: 10.1016/j.ijantimicag.2011.11.011
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.
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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.
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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.
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ABSTRACT: Pneumococcal infections, including pneumonia and invasive disease (IPD), are major sources of morbidity and mortality worldwide. Prevention of first acquisition of S. pneumoniae with the use of vaccines represents an effective method to reduce the burden of the disease in both children and adults. Two vaccines are currently available in adults: a pneumococcal polysaccharide vaccine (PPV23) that includes 23 purified capsular polysaccharide antigens and a pneumococcal protein-conjugate vaccine (PCV13) that includes capsular polysaccharide antigens covalently linked to a non-toxic protein. The PPV23 induces a humoral immune response and since it has been licensed, it has been the subject of debates and controversies. Numerous studies and meta-analyses have shown that PPV23 protects against IPD, although there are conflicting data regarding its efficacy for the prevention of pneumonia. Vaccination with PCV13 stimulates good antibody responses as well as mucosal antibody and suppresses colonization. A conjugate vaccine can be expected to have benefits over a polysaccharide vaccine, due to the characteristics of a T-cell dependent response in terms of affinity, maturation of antibodies with repeated exposure, induction of immunological memory and long lasting immunity. The PCV13 has demonstrated all these characteristics in children and fundamental differences in adults are not expected. The efficacy in adults is currently being investigated and results will be available soon. This article is protected by copyright. All rights reserved.
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