Michael Kresken

In Vitro Spectrum of Activity of Finafloxacin, a Novel, pH-Activated Fluoroquinolone, under Standard and Acidic Conditions

ABSTRACT Finafloxacin is a novel fluoroquinolone that exhibits enhanced antibacterial activity under acidic conditions. The aim of this study was to define the in vitro pH-activity relationship. Finafloxacin exhibited optimal antibacterial activity between pH 5.0 and 6.0 at which MICs were 4- to 8-fold lower than those determined at neutral pH. These observations were then confirmed against a larger collection of bacteria. These data suggest that finafloxacin could potentially offer a therapeutic advantage within acidic foci of infection.

Occurrence of multidrug resistance to oral antibiotics among Escherichia coli urine isolates from outpatient departments in Germany: Extended-spectrum β-lactamases and the role of fosfomycin

The in vitro activities of fosfomycin and seven other antibiotics commonly used for oral treatment of urinary tract infections (UTIs) were evaluated for 499 Escherichia coli isolated from urine samples during a nationwide laboratory-based surveillance study in 2010. Overall, the highest resistance rates were found for amoxicillin (42.9%), followed by amoxicillin/clavulanic acid (32.7%), trimethoprim/sulfamethoxazole (SXT) (30.9%), ciprofloxacin (19.8%), cefuroxime (10.0%), cefpodoxime (8.6%) and cefixime (8.2%). One-half of the isolates (n=252; 50.5%) were fully susceptible to the eight drugs, whilst only 6 strains (1.2%) were resistant to fosfomycin. Combined resistance to amoxicillin, cefuroxime, ciprofloxacin and SXT was detected in 29 isolates (5.8%). Moreover, 40 isolates (8.0%) produced an extended-spectrum β-lactamase (ESBL), including CTX-M-type ESBLs detected in 39/40 isolates (97.5%) and a TEM-52 ESBL in 1 strain (2.5%). The predominant CTX-M-type ESBL was CTX-M-15 (27/39; 69.2%). Of the 27 CTX-M-15 producers, 19 (70.4%) belonged to the clonal lineage E. coli O25b-ST131. All but one ESBL-producing strains were fosfomycin-susceptible. In view of the emergence of multidrug resistance to standard oral antibiotics, these data support that oral fosfomycin (trometamol salt) may represent a valuable option in the treatment of uncomplicated UTIs.

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 β-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.

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

ABSTRACT 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. agalactiaeand 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 [MIC50], 0.5 mg/liter; MIC90, 1 mg/liter, MIC range, 0.25 to 4 mg/liter).

High Prevalence of the ermB Gene among Erythromycin-Resistant Streptococcus pneumoniae Isolates in Germany during the Winter of 2000-2001 and In Vitro Activity of Telithromycin

ABSTRACT Of 595 isolates of Streptococcus pneumoniae from outpatients with respiratory tract infections, collected from 17 microbiology laboratories, 14.1% were resistant to erythromycin. Eighty-three erythromycin-resistant isolates were genetically analyzed, 83.1% of which harbored the ermB gene. Only four isolates (4.8%) harbored the mefA gene. Telithromycin exhibited potent activity against all isolates.

In vitro activities of ceftobiprole combined with amikacin or levofloxacin against Pseudomonas aeruginosa: evidence of a synergistic effect using time?kill methodology

Ceftobiprole is an investigational intravenous broad-spectrum cephalosporin with in vitro activity against Gram-positive and Gram-negative pathogens, including meticillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. Pseudomonas aeruginosa is a frequent nosocomial pathogen, increasingly associated with complicated skin and skin-structure infections. Combination antimicrobial therapy is recommended as empirical therapy for serious infections where P. aeruginosa is suspected. Therefore, in this study the interaction of ceftobiprole with two other antipseudomonal agents (amikacin and levofloxacin) was investigated. Time-kill studies were performed for each single agent and for the combination of ceftobiprole 4 mg/L with either amikacin or levofloxacin at 0.5×, 1× and 2× the minimum inhibitory concentration. Five clinical isolates of P. aeruginosa as well as the P. aeruginosa ATCC 27853 reference strain were tested at initial inocula of 5×10(5) colony-forming units (CFU)/mL (low inoculum) or 5×10(7) CFU/mL (high inoculum). Synergy was defined as a decrease of ≥2log(10) CFU/mL with the combination compared with the most active single drug at 6 h and 24 h. At low inoculum with ceftobiprole as a single agent, viable counts were decreased by 1.5-2log(10) at 6 h. Addition of either amikacin or levofloxacin resulted in synergistic bactericidal activity at 24 h. At high inoculum the combination of ceftobiprole with amikacin or levofloxacin demonstrated synergism in one of three and three of five strains, respectively. This study demonstrated that the combination of ceftobiprole at a clinically achievable concentration of 4 mg/L with amikacin or levofloxacin exhibited synergistic activity against P. aeruginosa. There was no evidence of antagonism for either combination.

In Vitro Activity of Nitroxoline against Escherichia coli Urine Isolates from Outpatient Departments in Germany

Increased acquired resistance to orally administered antibiotics in Escherichia coli has complicated the management of urinary tract infections (UTI) in outpatients ([1][1][–][2][3][3]). In this context, nitroxoline (5-nitro-8-hydroxyquinoline) ([Fig. 1][4]), an oral antibiotic, has received

In-vitro activity of ceftolozane/tazobactam against pseudomonas aeruginosa and enterobacteriaceae isolates recovered from hospitalized patients in germany

To evaluate the activity of ceftolozane/tazobactam compared with other broad-spectrum antimicrobials against Pseudomonas aeruginosa and Enterobacteriaceae, 497 non-duplicate P. aeruginosa and 802 Enterobacteriaceae clinical isolates were consecutively collected during the period from September 2014 to April 2015 from patients in Germany with bloodstream, lower respiratory tract, intra-abdominal or urinary tract infections. Antimicrobial susceptibility testing was performed by broth microdilution. Results were interpreted according to EUCAST criteria. Ceftolozane/tazobactam showed good activity against Escherichia coli and Klebsiella pneumoniae isolates with MIC50/90 values of 0.25/0.5 mg/L and 0.25/1 mg/L, respectively. Comparatively, piperacillin/tazobactam, ceftazidime and meropenem MIC50/90 values were 2/8 mg/L, 0.25/8 mg/L and ≤0.03/ ≤ 0.03 mg/L, respectively, for E. coli, and 2/16 mg/L, 0.12/8 mg/L, and ≤0.03/ ≤ 0.03 mg/L, respectively, for K. pneumoniae isolates. The activity of ceftolozane/tazobactam against P. aeruginosa was superior to that of other antipseudomonal antimicrobials. Based on MIC50/90 values, ceftolozane/tazobactam (0.5/2 mg/L) was more active than piperacillin/tazobactam (8/64 mg/L), ceftazidime (2/16 mg/L), cefepime (2/16 mg/L) or meropenem (0.5/8 mg/L). In conclusion, ceftolozane/tazobactam exhibited the best in vitro potency of the antibiotics tested against P. aeruginosa, including isolates that were resistant to piperacillin/tazobactam, cefepime, ceftazidime, doripenem, meropenem, ciprofloxacin, levofloxacin, amikacin, and tobramycin. Ceftolozane/tazobactam has the potential to become a useful addition to the limited armamentarium of drugs that can be used to treat this problem pathogen.

Antimicrobial susceptibility of bacterial isolates from patients presenting with ear, nose and throat (ENT) infections in the German community healthcare setting

Empiric initial antibiotic therapy of bacterial infections is based primarily upon the susceptibility of the most common causative pathogens. The purpose of this study was to provide susceptibility data on six bacterial species known to cause ear, nose and throat (ENT) infections. A total of 1066 isolates collected during a nationwide laboratory-based surveillance study were analysed. All Streptococcus pyogenes isolates were penicillin (PEN)-susceptible, indicating that natural penicillins can still be recommended as the first-line treatment for group A streptococcal tonsillopharyngitis. Of the S. pneumoniae isolates, 92.9% were PEN-susceptible and of the Haemophilus influenzae isolates, 89.7% were amoxicillin-susceptible, retaining aminopenicillins as the first-line treatment for acute otitis media (AOM) and acute rhinosinusitis (ARS), in case antibiotic therapy is considered. In contrast, cefuroxime axetil seems less likely to be suitable for the treatment of AOM or ARS, as all Moraxella catarrhalis and >99% of the H. influenzae isolates were categorised as intermediate or resistant. The susceptibility rates of Pseudomonas aeruginosa were 97–100% for the drugs tested, except for the fluoroquinolones (87.6%). Overall, bacterial isolates from outpatients presenting with ENT infections showed low frequencies of resistance in Germany. However, given the emergence of multidrug resistance to standard antibiotics in Escherichia coli and other pathogens, inappropriate use of broad-spectrum antibiotics for the treatment of ENT infections has to be avoided.

In-vitro-Aktivität von Mecillinam gegen Escherichia coli: Urinisolate von Patienten im niedergelassenen Versorgungsbereich in Deutschland

National and international guidelines recommend fosfomycin trometamol, nitrofurantoin, nitroxoline, and pivmecillinam as first-line agents for the treatment of acute uncomplicated cystitis. Escherichia coli is by far the leading cause of community-acquired urinary tract infections. Pivmecillinam (X-SYSTO®) is an oral prodrug of mecillinam, a penicillin derivative that was reintroduced to the German market in March 2016. This study aimed to investigate the proportion of mecillinam-resistant strains among E. coli isolates prior to the introduction of X-SYSTO® in Germany.An in-vitro study was carried out to determine the minimal inhibitory concentrations (MICs) of mecillinam against 494 urine isolates of E. coli (including multidrug-resistant strains). Isolates were obtained from outpatients and collected in 25 laboratories between October and December 2013. MIC breakpoints defined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) were applied for classifying the bacterial isolates as mecillinam-susceptible (MIC ≤ 8 mg/l) or resistant (MIC > 8 mg/l).The concentrations of mecillinam needed to inhibit 50 % and 90 % of the test isolates were 1 and 4 mg/l, respectively, for isolates displaying the extended spectrum β-lactamase phenotype, and 0.25 and 4 mg/l, respectively, for the remaining isolates. Overall, 98 % of the isolates were found to be mecillinam-susceptible (MIC ≤ 8 mg/l), and 2 % were found to be resistant (MIC > 8 mg/l).These findings support the recommendation to regard pivmecillinam as a first-line option for the treatment of acute uncomplicated cystitis.