Antimicrobial resistance patterns in respiratory pathogens isolated in an Italian university hospital during a period of eight years: a statistical analysis.

The antimicrobial resistance patterns of respiratory pathogens isolated during an 8-year period (1990-1997) in an Italian hospital from patients with bronchopulmonary infections were investigated. A global variation in the resistance of Staphylococcus aureus to all relevant antibiotics was observed during the years 1990-1997. With the exception of penicillin and amoxicillin, to which Staphylococci were always resistant, and vancomycin, to which they were always susceptible, in the first period (1990-1992) the percentage of resistance to beta-lactams, aminoglycosides, macrolides, fluoroquinolones and cotrimoxazole was about 15%, while in the last period (1993-1997) it was about 35%. No global variation in resistance to the antimicrobials examined during the study period was observed for gram-negative bacteria. The percentages of resistance to the more recent beta-lactams, aminoglycosides and fluoroquinolones were generally less than 10% for the KES group, less than 20% for Pseudomonas aeruginosa, and less than 30% for other Pseudomonas species. A high percentage of resistance was observed for the KES group to amoxicillin + clavulanic acid (60%) and to cefoxitin (48%).

Effect of different beta-lactams in combination with beta-lactamase inhibitors in the presence or absence of tobramycin against some enterobacteriaceae producing extended-spectrum beta-lactamases.

Extended-spectrum beta-lactamase (ESBL) production among members of the family Enterobacteriaceae generally involves resistance to oxyimino-cephalosporins and monobactams, while implying different susceptibility profiles with other antimicrobial agents. We have investigated the activity of some beta-lactam antibiotics, alone or in double and triple combinations with beta-lactamase inhibitors, in the presence or absence of tobramycin (TOB), against some Enterobacteriaceae producing ESBL by means of time-kill curves. Antimicrobials employed were ceftazidime (CAZ), cefotaxime (CTX), TOB, ampicillin (AMP), ampicillin-sulbactam (ASL), amoxicillin (AML), amoxicillin-clavulanic acid (AMC), piperacillin (PIP) and piperacillin-tazobactam (TZP), at 1/4 minimum inhibitory concentration for susceptible strains and at achievable serum concentrations for resistant strains. Only the combinations CTX-ASL, CAZ-ASL and PIP-ASL were synergistic, both at 6 and 24 h, on some strains of Klebsiella species.

Effect of different combinations of sparfloxacin, oxacillin, and fosfomycin against methicillin-resistant staphylococci.

The in vitro activity of combinations of sparfloxacin/oxacillin, sparfloxacin/fosfomycin, and oxacillin/fosfomycin was investigated against 16 methicillin-resistant Staphylococcus aureus (MRSA) isolates and 12 methicillin-resistant Staphylococcus epidermidis (MRSE) isolates moderately resistant to sparfloxacin. Synergic interactions were observed more frequently against MRSE than against MRSA strains. The most effective combination on both species was fosfomycin plus oxacillin, synergistic against ten of 16 MRSA and eight of 12 MRSE strains.

Comparative antimicrobial activity and post-antibiotic effect of azithromycin, clarithromycin and roxithromycin against some respiratory pathogens.

Recent macrolide derivatives, roxithromycin, azithromycin and clarithromycin show more favourable pharmacokinetic characteristics in comparison to old ones and some differences in antibacterial activity. With the aim of improving our understanding of some aspects of their action against respiratory pathogens, we determined the MICs and MBCs of Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, Moraxella catarrhalis and Haemophilus influenzae. Azithromycin was the most active agent against Haemophilus influenzae and Moraxella catarrhalis, while clarithromycin was more active against Streptococcus pneumoniae, Streptococcus pyogenes and Staphylococcus aureus with MICs similar to those of erythromycin. The bactericidal activity of all tested derivatives was weak against Staphylococcus aureus (MBC/MIC ratio approximately 16) and against Moraxella catarrhalis (MBC/MIC ratio, 8-16), but good against Staphylococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae (MBC/MIC ratio, 2-4). The determination of killing curves in the presence of 2 MIC and 10 MIC of azithromycin, clarithromycin and roxithromycin confirmed their weak bactericidal activity against Staphylococcus aureus and Moraxella catarrhalis as well as their effective activity against Streptococcus pyogenes and Streptococcus pneumoniae. Azithromycin showed the highest bactericidal activity against Haemophilus influenzae. As expected, the three derivatives produced a quite prolonged PAE when exposed to 5 MIC for 1 h, ranging between 2-4 h. The bactericidal activity and the prolonged PAE of new macrolides for the most common respiratory pathogens should assure a good clinical activity in respiratory infections including those sustained by Haemophilus influenzae, which is less susceptible to erythromycin and other old macrolides.

High-level gentamicin-resistant enterococci: in vitro activity of double and triple combinations of antimicrobial drugs.

The ability of double and triple combinations of antimicrobials with different mechanisms of action, such as teicoplanin, meropenem, gentamicin and sparfloxacin, to achieve synergisms was investigated in vitro on some moderate-level gentamicin-resistant (MLGR: 8 < or = MIC < or = 256 mg/l) and high-level gentamicin-resistant (HLGR: MIC > 500 mg/l) enterococci. On MLGR strains, a constant synergistic effect was achieved by a combination of teicoplanin with gentamicin or with meropenem, while generally addition, sometimes close to synergism, was exhibited by gentamicin-meropenem, gentamicin-sparfloxacin and teicoplanin-sparfloxacin associations. Triple combinations of teicoplanin, meropenem and gentamicin, or teicoplanin, sparfloxacin and gentamicin, always showed a remarkable advantage in terms of synergism over double combinations. On HLGR enterococci, the only double association showing an additive effect, sometimes close to synergism, was teicoplanin plus meropenem, while the triple combination of teicoplanin with gentamicin and meropenem always showed a marked synergistic effect. An effect very close to synergism was also shown by the combination of teicoplanin with sparfloxacin and gentamicin.