Sorption and biodegradation of selected antibiotics in biosolids.
Antimicrobial efficacy is measured in vitro by determination of minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of antimicrobials, but these values do not account for fluctuations of drug concentrations within the body or the time course of the drug's in vivo antibacterial activity. However, in vivo bacteriologic efficacy can be predicted by pharmacokinetic/pharmacodynamic (PK/PD) parameters, such as the time for which the serum drug concentration is above the MIC (T>MIC), the ratio of peak serum concentration to the MIC, and the ratio of the area under the 24-h serum concentration-time curve to the MIC (AUC/MIC). Different patterns of antibacterial activity correlate with different PK/PD parameters. For example, a T>MIC of 40-50% of the dosing interval is a good predictor of bacteriologic efficacy for penicillins, cephalosporins, and most macrolides, and an AUC/MIC ratio of at least 25 is required for efficacy with fluoroquinolones and azalides. The PK/PD breakpoint for susceptibility of an organism to a specific dosing regimen of an agent can be determined as the highest MIC met by the relevant PK/PD parameter for bacteriologic efficacy for that agent. These parameters have been validated extensively in animal models, as well as in many human studies where bacteriologic outcome has been determined. The PK/PD breakpoint of an agent is determined primarily by the dosing regimen, and generally applies to all pathogens causing disease at sites where extracellular tissue levels are similar to non-protein-bound serum levels. On this basis, many parenteral beta-lactams are active against almost all strains of Streptococcus pneumoniae, including 'penicillin-non-susceptible' strains, in all body sites except for the central nervous system. Application of PK/PD breakpoints to standard dosing regimens of oral beta-lactams predicts that agents such as cefaclor and cefixime will have efficacy only against penicillin-susceptible strains of S. pneumoniae, while cefuroxime axetil, cefpodoxime and cefdinir will be effective against all penicillin-susceptible as well as many penicillin-intermediate strains. However, the most active oral beta-lactams, amoxicillin and amoxicillin-clavulanate, have predicted efficacy against all penicillin-susceptible and -intermediate pneumococci, as well as against most penicillin-resistant strains, at amoxicillin doses of 45-90 mg/kg per day in children and 1.75-4.0 g/day in adults. These predictions are supported by evidence from animal studies of bacteriologic efficacy. The use of PK/PD parameters to predict bacterial eradication therefore allows an evidence-based approach to the selection of appropriate antimicrobial therapy.
In Rijeka, 35 different systemic antibiotics were used and in Smolensk 22. The overall consumption of antibiotic drugs in Rijeka was more than three times higher than in Smolensk (28.96 vs 8.3 DDD/100 bed-days). The top five antibiotic drugs used in Smolensk were amoxicillin, mydecamicin, ampicilin, doxycylin, gentamicin; and in Rijeka cefuroxime axetil, ceftriaxone, azytromycin, ceftibuten and amoxicillin.
Doxycycline and cefuroxime axetil had comparable efficacy. At both 6 and 12 months, the frequency of new or increased symptoms in patients with erythema migrans did not exceed the frequency of such symptoms in a control group of individuals of similar gender and age without a clinical history of Lyme disease. At 12 months after enrollment, only 5 (2.2%) of 230 evaluable patients reported new or increased symptoms, and in none of the patients were these symptoms of sufficient severity to be functionally disabling.
Acute otitis media (AOM) is not only the most common bacterial infection in children in the United States, it is also the most common indication for the prescription of antibiotics. Unfortunately, antibiotic resistance to pathogens (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis) typically causative of AOM, continues to increase. More than 30% of the beta-lactamase producing H. influenzae are resistant to amoxicillin and virtually all strains of M. catarrhalis are beta-lactamase-positive. The emergence of multidrug-resistant strains, particularly S. pneumoniae, complicates the management of AOM and increases the risk for treatment failure. Because of growing resistance, the Centers for Disease Control and the American Academy of Pediatrics promote the judicious use of antibiotics in the treatment of AOM. Their recommendations emphasize the importance of distinguishing AOM from otitis media with effusion, minimizing the use of antibiotics, and discerning between first- and second-line antibiotics in the treatment of simple uncomplicated AOM versus non-responsive/recurrent AOM. Because spontaneous cure rates are lower in complicated AOM and AOM secondary to S. pneumoniae infection, antibiotic therapy remains an appropriate treatment option for most children with AOM. When amoxicillin, the treatment of choice in AOM, is not effective or not tolerated in children, the prescriber should consider an alternative that displays not only excellent antimicrobial activity against the suspected pathogens, but also characteristics, such as convenient dosing, tolerability, and palatability, that promote compliance and adherence in children. The cephalosporins offer an alternative to penicillins. Cephalosporins such as cefuroxime axetil (second-generation) and cefdinir and cefpodoxime proxetil (third-generation), offer a broad spectrum of activity and are approved for use in a convenient once- or twice-daily dosing schedule, thus increasing the likelihood of compliance with the full course of therapy. Cefdinir is a possible second-line alternative to amoxicillin for children with AOM, particularly among children who are likely to be noncompliant with a two- to three-times-daily dosing schedule, and those instances where there is a high likelihood for, or a known infection with an amoxicillin-resistant pathogen.