Increase of beta-Lactam-Resistant Invasive Haemophilus influenzae in Sweden, 1997 to 2010

The proportions of Haemophilus influenzae resistant to ampicillin and other beta-lactam antibiotics have been low in Sweden compared to other countries in the Western world. However, a near-doubled proportion of nasopharyngeal Swedish H. influenzae isolates with resistance to beta-lactams has been observed in the last decade. In the present study, the epidemiology and mechanisms of antimicrobial resistance of H. influenzae isolates from blood and cerebrospinal fluid in southern Sweden from 1997 to 2010 (n = 465) were studied. Antimicrobial susceptibility testing was performed using disk diffusion, and isolates with resistance to any tested beta-lactam were further analyzed in detail. We identified a significantly increased (P = 0.03) proportion of beta-lactam-resistant invasive H. influenzae during the study period, which was mainly attributed to a significant recent increase of beta-lactamase-negative beta-lactam-resistant isolates (P = 0.04). Furthermore, invasive beta-lactamase-negative beta-lactam-resistant H. influenzae isolates from 2007 and onwards were found in higher proportions than the corresponding proportions of nasopharyngeal isolates in a national survey. Multiple-locus sequence typing (MIST) of this group of isolates did not completely separate isolates with different resistance phenotypes. However, one cluster of beta-lactamase-negative ampicillin-resistant (BLNAR) isolates was identified, and it included isolates from all geographical areas. A truncated variant of a beta-lactamase gene with a promoter deletion, bla(TEM-1)-P Delta dominated among the beta-lactamase-positive H. influenzae isolates. Our results show that the proportions of beta-lactam-resistant invasive H. influenzae have increased in Sweden in the last decade

Pharmacodynamics of moxifloxacin and levofloxacin against Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli: simulation of human plasma concentrations after intravenous dosage in an in vitro kinetic model.

Objectives: To compare in an in vitro kinetic model the pharmacodynamics of moxifloxacin and levofloxacin with a concentration-time profile simulating the human free non-protein bound concentrations of 400 mg moxifloxacin intravenous (iv) once daily, 500 mg levofloxacin iv once daily and 750 mg levofloxacin iv once daily against strains of Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli with variable susceptibility to fluoroquinolones. Methods: The strains used in the study included S. pneumoniae ATCC 6306 (native strain), S. pneumoniae 19397 (double mutation; gyrA and parC), S. pneumoniae 4241 (single mutation; parC), S. aureus ATCC 13709 (native strain), S. aureus MB5 (single mutation; gyrA), E. coli M12 (single mutation; gyrA), E. coli ATCC 25922 (native strain) and K. pneumoniae ATCC 29655 (native strain). The strains were exposed to moxifloxacin and levofloxacin in an in vitro kinetic model simulating the free human serum concentration-time profile of moxifloxacin 400 mg once daily, levofloxacin 500 mg once daily and 750 mg once daily. Repeated samples were taken regularly during 24 h and viable counts were carried out. Results and conclusions: A correlation was seen between both the area under the serum concentration curve and MIC (AUC/MIC) and the peak concentration/MIC (C-max/MIC) versus area under the bactericidal killing curve (AUBKC) or Delta log(0-24) cfu/mL. Compiling all data, an AUC/MIC of similar to 100 and a Cmax/MIC of 10 gave a maximal bactericidal effect for both levofloxacin and moxifloxacin. In accordance with the results from others, our study indicated that a lower AUC/MIC was needed for S. pneumoniae in comparison with the Gram-negative bacteria studied. Moxifloxacin yielded higher AUC/MIC and Cmax/MIC against the investigated Gram-positive bacteria in comparison with levofloxacin 500 mg once daily and 750 mg once daily

Pharmacodynamic studies of amoxicillin against Streptococcus pneumoniae: comparison of a new pharmacokinetically enhanced formulation (2000 mg twice daily) with standard dosage regimens

Objectives: To compare the pharmacodynamic effects of a pharmacokinetically enhanced formulation of amoxicillin 2000 mg twice daily, with amoxicillin 875 mg twice daily, 875 mg three times daily and 500 mg three times daily against Streptococcus pneumoniae with different susceptibility to amoxicillin in an in vitro kinetic model. Methods: Strains of S. pneumoniae with amoxicillin MICs of 1, 2, 4 and 8 mg/L at an initial inoculum of approximately 10(5) cfu/mL were exposed to amoxicillin in an in vitro kinetic model simulating the human serum concentration-time profile of the pharmacokinetically enhanced formulation twice daily (C-max 17 mg/L after 1.5 h). All isolates were also exposed to amoxicillin with concentration-time profiles correlating to the human dosage of 875 mg twice daily (C-max 15 mg/L after 1 h), 875 mg three times daily and 500 mg (C-max 8 mg/L after 1 h) three times daily with simulated half-life of 1 h. Repeated samples were taken regularly during 24 h and viable counts were carried out. Results: Overall, the pharmacokinetically enhanced formulation was more effective at reducing bacterial counts than any of the other formulations evaluated. Eradication was achieved with the enhanced formulation for strains with a MIC of less than or equal to2 mg/L, however, regrowth occurred with the other dosing regimens. In the experiments with the strain with a MIC of 4 mg/L, the enhanced formulation kept the bacterial counts less than or equal to10(2) cfu/mL for at least 14 out of 24 h tested. In contrast, none of the other formulations reduced the bacterial counts down to less than or equal to10(2) cfu/mL at any point. None of the regimens was able to eradicate the strain with an MIC of 8 mg/L, even though an initial substantial kill was noted with the enhanced formulation after both doses. The least effective dosage regimen for all strains was 875 mg twice daily

Behandling av patienter med hud- och mjukdelsinfektioner. Resultat av STRAMAs diagnos- och receptundersokning bland allmanlakare

n one week of November 2000 and 2002, a diagnosis-antibiotic prescribing study was performed in general practice in 5 counties in Sweden. In total 11 515 patients were registered with a diagnosis of an infectious disease. Skin- and soft tissue infections were responsible for 10% of the visits and 13% of the antibioitc prescriptions. Older people (> 65 years) had more skin- and soft tissue infections in comparison to younger people. A high percentage of the patients received antibiotics

Pharmacodynamic studies of vancomycin, metronidazole and fusidic acid against Clostridium difficile

Background: Pharmacodynamic studies of antibiotics have attracted great interest in recent years. However, studies on the pharmacodynamics of different antibiotics against Clostridium difficile are scarce. Methods: The postantibiotic effects (PAE) and the postantibiotic sub-minimum inhibitory concentration (MIC) effects (PA SME) of vancomycin, metronidazole and fusidic acid were investigated by viable counts against three different strains of C. difficile. The killing rate and extent of the three antibiotics against the same strains were also studied by adding 2, 4, 8, 16 and 32 ! MIC of the three antibiotics, respectively. Results: Metronidazole exerted a very rapid bactericidal effect at concentrations of 8 ! MIC and above against all three strains investigated. Vancomycin gave overall less kill in comparison to metronidazole and was bacteriostatic against two of the three strains. Fusidic acid exerted a concentration-dependent killing against two of the strains. Vancomycin exerted short PAEs and PA SMEs against all three strains. Significantly longer PAEs and PA SMEs were noted for fusidic acid. Metronidazole gave similar short PAEs like vancomycin but longer PA SMEs were noted against two of the investigated strains. Conclusion: Metronidazole exerted the most prominent bactericidal effect greater than fusidic acid and greater than vancomycin. Fusidic acid gave overall the longest PAEs and PA SMEs greater than metronidazole and greater than vancomycin. Copyright (C) 2007 S. Karger AG, Basel

Upper respiratory tract infections in general practice: Diagnosis, antibiotic prescribing, duration of symptoms and use of diagnostic tests

A diagnosis/antibiotic prescribing study was performed in 5 counties in Sweden for 1 week in November 2000. As part of this study, the characteristics and clinical management of patients with upper respiratory tract infections ( n = 2899) in primary care were analyzed. Almost half of the patients were aged < 15 y and one-fifth of the patients consulted out of hours. Of all patients seeking primary care for upper respiratory tract infections, 56.0% were prescribed an antibiotic. Almost all patients who were given the diagnoses streptococcal tonsillitis, acute otitis media or acute sinusitis were prescribed antibiotics, compared to 10% of patients with common cold or acute pharyngitis. The most frequently prescribed antibiotic was penicillin V (79.2%) and this was even more pronounced out of hours, when the diagnoses otitis media and streptococcal tonsillitis were more frequently used. In patients with common cold and acute pharyngitis, the percentage who received antibiotics increased with increasing length of symptoms and increasing CRP levels. In patients with acute pharyngitis or streptococcal tonsillitis, antibiotics were prescribed less frequently provided streptococcal tests were performed. The management of patients with upper respiratory tract infections in general practice seems to be in good agreement with current Swedish guidelines. However, the study indicates some areas for improvement. The diagnosis of acute sinusitis seems to have been overestimated and used only to justify antibiotic treatment