Susceptibility of common aerobic pathogens to tigecycline: results of a surveillance study in Germany.

Tigecycline is a novel antimicrobial agent for parenteral use encompassing a broad spectrum of bacterial pathogens, including multi-resistant organisms. Here, we report the results of the first nationwide surveillance trial that was conducted in order to evaluate the susceptibility of bacterial isolates to tigecycline in a European country prior to its clinical use. A total of 2,610 Gram-positive and Gram-negative organisms recovered from hospitalized patients were tested. Minimum inhibitory concentrations (MICs) were determined using the microdilution method. All enterococci, staphylococci (including methicillin-resistant Staphylococcus aureus; MRSA), and streptococci tested were tigecycline-susceptible, except one isolate of Staphylococcus haemolyticus. Among the Gram-negative bacteria, 100% of the Escherichia coli isolates (including extended spectrum beta-lactamase [ESBL]-producers) were tigecycline-susceptible, while about 10% of the Enterobacter cloacae and Klebsiella pneumoniae isolates were resistant. Based on the results of this surveillance study, tigecycline may represent a suitable option most notably for the empiric treatment of bacterial mixed infections, including in clinical situations in which multi-resistant organisms are suspected.

Bactericidal activity of daptomycin, vancomycin, teicoplanin and linezolid against Staphylococcus aureus, Enterococcus faecalis and Enterococcus faecium using human peak free serum drug concentrations.

The bactericidal activities of daptomycin, vancomycin, teicoplanin and linezolid at human peak free serum concentrations (C(max,free)) were determined against Staphylococcus aureus (one methicillin-susceptible and two methicillin-resistant strains), Enterococcus faecalis and Enterococcus faecium (one vancomycin-susceptible and one vancomycin-resistant strain of each). Daptomycin was rapidly bactericidal against 7/7 strains at C(max,free) of 22.0 mg/L (corresponding to 63% protein binding) and against 3/7 strains at 4.8 mg/L (corresponding to 92% protein binding). Vancomycin (18.0 mg/L) was bactericidal against only two strains. Both teicoplanin (4.5 mg/L) and linezolid (10.4 mg/L) were consistently bacteriostatic. Daptomycin is a useful option for the treatment of Gram-positive infections owing to its strong bactericidal activity.

Activities of various beta-lactams and beta-lactam/beta-lactamase inhibitor combinations against Acinetobacter baumannii and Acinetobacter DNA group 3 strains.

Acinetobacter baumannii and Acinetobacter DNA group 3 are members of the so-called A. calcoaceticus-A. baumannii complex and are important nosocomial pathogens. Multiresistance in these organisms is increasingly frequent, and alternative treatment options are needed. The beta-lactamase inhibitors clavulanate, sulbactam and tazobactam have intrinsic activity against Acinetobacter strains. In the present study, broth microdilution was used to assess the in-vitro activities of currently available beta-lactam/beta-lactamase inhibitor combinations and sulbactam alone against 469 Acinetobacter isolates (A. baumannii, n=395; Acinetobacter DNA group 3, n=74) collected from various laboratories in Germany. Fixed concentrations and fixed ratios of beta-lactamase inhibitors were used. Sulbactam-containing combinations (susceptibility rates of 90.4-92.7% for A. baumannii and 97.3-100% for Acinetobacter DNA group 3) and sulbactam alone were superior to clavulanate- and tazobactam-containing combinations. The activity of sulbactam-containing combinations against members of the A. calcoaceticus-A. baumannii complex was conferred exclusively by the intrinsic activity of the beta-lactamase inhibitor and did not result from enhanced beta-lactam activity. Testing with the inhibitor added at a fixed ratio of inhibitor to beta-lactam appeared to give more reliable results than testing at a fixed concentration of the inhibitor. Resistance to carbapenems (0.3%) remains low in Germany.

Surveillance of linezolid resistance in Germany, 2001-2002.

A surveillance study was performed throughout Germany from November 2001 to June 2002 to assess the prevalence of linezolid-resistant isolates among Gram-positive bacteria from routine susceptibility data and to compare the in-vitro activity of linezolid to that of other antibacterial agents. Each of 86 laboratories provided routine susceptibility data for 100 consecutive isolates. Most laboratories (c. 60%) used the disk diffusion test. Laboratories were also requested to send a representative sample of their isolates, as well as all isolates reported as intermediate or resistant to linezolid, to a reference laboratory for MIC determination. Susceptibility data for 8594 isolates were evaluated. Sites of infection were skin and soft tissue (29.9%), upper and lower respiratory tract (19.1%), foreign body or catheter (10.5%), or urinary tract (9.8%). Routine linezolid susceptibility data were reported for 6433 isolates. The prevalence of linezolid resistance, as reported to the clinician, was 0.4% in Staphylococcus aureus, 0.3% in Staphylococcus epidermidis, 2.9% in Enterococcus faecalis, 2.3% in Enterococcus faecium, 1.4% in Streptococcus pyogenes and 2.9% in Streptococcus agalactiae. Linezolid resistance was not detected in Streptococcus pneumoniae or in viridans group streptococci. Sixty-nine of 115 isolates reported as intermediate or resistant to linezolid were retested, but none was resistant to linezolid. Linezolid exhibited excellent in-vitro activity against representative isolates of the six most frequently encountered species (MIC90, 1-2 mg/L). The prevalence of resistance to linezolid was very low in Germany. Organisms reported as linezolid-resistant should be retested, either in the same laboratory with an alternative method or in a reference laboratory.

Efficacy and safety of 2% mupirocin ointment in the treatment of primary and secondary skin infections--an open multicentre trial.

Staphylococci and beta-haemolytic streptococci are usually responsible for causing common primary and secondary skin infections. Mupirocin (Bactroban, Eismycin; trademarks of Beecham Group plc), a new antibiotic unrelated to any other antibacterial agent and developed for topical use only, shows a high level of activity against these bacteria. In an open multicentre study the efficacy and safety of mupirocin (2% in a polyethylene glycol vehicle) was evaluated in 1,391 general practice patients with superficial skin infections. The most common skin infections treated were pyoderma (eg, impetigo, folliculitis) and secondarily infected skin lesions. Treatment consisted of application of the ointment three times daily for an average of nine days. A total of 1,304 patients were evaluable for post-treatment clinical assessment. At the end of the treatment 961 (73.7 per cent) patients were cured and in 293 (22.5 per cent) patients the symptoms of the infection had markedly improved. In total, 525 bacterial strains were isolated from the wounds of 445 patients, predominantly staphylococci (n = 344) and streptococci (n = 93). Local side effects such as burning, itching and reddening were observed in 39 (2.9 per cent) of 1,357 patients. No evidence of systemic toxicity or abnormal laboratory data was noted. Mupirocin 2% ointment proved to be effective and safe in the treatment of primary and secondary skin infections.

[beta-lactam-antibiotics in the treatment of community-acquired respiratory tract infections with penicillin-resistant pneumococci]. / beta-Lactam-Antibiotika in der Therapie von ambulant erworbenen Atemwegsinfektionen mit Penicillin-resistenten Pneumokokken.

Streptococcus pneumoniae is still the most important pathogen of community-acquired respiratory tract infections. During the last decades in many countries an increase in the spread of antibiotic resistant strains (e. g. against beta-lactams, macrolides, tetracyclin) was observed. Resistance against penicillin is often associated with resistance against macrolides and other antibiotic classes. In Germany surveillance studies including isolates from patients with community-acquired respiratory tract infections have shown that about 14 % of strains show a reduced susceptibility against penicillin (MIC-values 0.12 - 1 mg/L) and up to 4 % are highly resistant against penicillin (MIC >/= 2 mg/L). Resistance against tetracycline or macrolides was detected in up to 12 and 15 % of strains, respectively. According to the treatment guidelines of the Paul-Ehrlich-Gesellschaft für Chemotherapie and the Deutschen Atemwegsliga penicillins and cephalosporins are recommended as first line antibiotics for the treatment of community-acquired respiratory tract infections. As pneumococcal strains with reduced susceptibility against penicillin show often also a reduced susceptibility against cephalosporins the questions arises which beta-lactam antibiotics should still be used in empirical treatment of such strains. beta-Lactam-antibiotics highly differ in their in-vitro-activity against S. pneumoniae and their pharmacokinetic properties. In different models is has been demonstrated for beta-lactams that an adequate clinical and bacteriological efficacy is achievable when the serum levels of the free, i. e. not protein bound fraction of drug exceeds the MIC of the pathogen for at least 40 to 50 % of the dosing interval (T > MIC). In a clinical situation where pneumococci with reduced susceptibility against penicillin cannot be ruled out, only beta-lactam antibiotics with favourable pharmacological properties (good in-vitro activity, high and long lasting serum levels) should be used for treatment.

Nationwide German multicenter study on prevalence of antibiotic resistance in staphylococcal bloodstream isolates and comparative in vitro activities of quinupristin-dalfopristin.

Antibiotic-resistant gram-positive bacteria have become an increasing problem in the last two decades. In order to evaluate the prevalence of antibiotic resistance in staphylococcal bloodstream isolates in Germany, 2,042 staphylococci collected in 21 tertiary-care hospitals were investigated during a 3-year period (March 1996 to March 1999). Altogether, 1,448 S. aureus isolates and 594 coagulase-negative staphylococci (CoNS) that comprised 13 different species were included. Furthermore, the antistaphylococcal activities of quinupristin-dalfopristin were compared with those of eight other compounds by the broth microdilution method. The rates of oxacillin resistance in Staphylococcus aureus, S. epidermidis, S. haemolyticus, and other CoNS were 13.5, 69, 90, and 34%, respectively. In oxacillin-resistant strains high rates of resistance (up to 100%) to erythromycin, clindamycin, ciprofloxacin, and gentamicin were also observed. However, no strain appeared to be resistant to vancomycin or quinupristin-dalfopristin. The streptogramin combination exhibited excellent in vitro activity against all staphylococcal species tested, regardless of the patterns of resistance to other drug classes. In terms of MICs at which 90% of the isolates are inhibited, quinupristin-dalfopristin was 2 times more active against S. aureus isolates, 4 to 16 times more active against S. haemolyticus, and 8 to 32 times more active against S. epidermidis than vancomycin or teicoplanin.

Nationwide German multicenter study on the prevalence of antibiotic resistance in streptococcal blood isolates from neutropenic patients and comparative in vitro activities of quinupristin-dalfopristin and eight other antimicrobials.

In a prospective multicenter study (1996 to 1999), 156 episodes of bacteremic streptococcal infections of neutropenic patients were evaluated. Streptococcus oralis (26.3%), S. pneumoniae (26.3%), S. agalactiae (11.5%), S. mitis (9%), and S. pyogenes (5.8%) were the predominant species. Four strains (2.6%) were found to be intermediately resistant to penicillin. One strain (0.6%) was found to be highly resistant to penicillin (MIC, 8 mg/liter). Reduced susceptibility to penicillin was detected among S. oralis (14.6%), S. mitis (7.1%), and S. pneumoniae (4.9%) isolates but was not recorded among S. agalactiae and S. pyogenes. Resistance rates and intermediate resistance rates for other antimicrobials were as follows (all species): amoxicillin, 1.3 and 3.2%; erythromycin, 16 and 2.6%; clindamycin, 5.8 and 0%; ciprofloxacin, 1.9 and 7.7%. Quinupristin-dalfopristin showed good in vitro activity against most streptococcal isolates (MIC at which 50% of the isolates were inhibited [MIC(50)], 0.5 mg/liter; MIC(90), 1 mg/liter, MIC range, 0.25 to 4 mg/liter).