Inge Engels

Synergy of simultaneous administration of ofloxacin and granulocyte colony-stimulating factor in killing of Escherichia coli by human neutrophils

SummaryThein vitro effect of subinhibitory and inhibitory concentrations of ofloxacin and G-CSF on the bactericidal activity of polymorphonuclear leucocytes (PMNL) againstEscherichia coli was investigated. PMNL obtained from healthy volunteers were incubated with different concentrations of G-CSF and ofloxacin for 180 min. The minimum inhibitory concentration (MIC) of ofloxacin and even 1/4 × MIC enhanced the bactericidal activity of PMNL. G-CSF at a concentration of 6,000 units/ml led to a significant improvement of the bactericidal activity of PMNL. The combination of 6,000 units/ml of G-CSF and ofloxacin in inhibitory as well as subinhibitory concentrations, however, showed a significant synergistic effect on the antibacterial activity of PMNL during the complete incubation period. Combinations of G-CSF and antibiotics could therefore be beneficial for infected patients, especially those with impaired cellular host defense.ZusammenfassungWir untersuchtenin vitro die bakterizide Wirkung von neutrophilen Granulozyten in Kombination mit subinhibitorischen und inhibitorischen Konzentrationen von Ofloxacin und G-CSF aufEscherichia coli. Neutrophile Granulozyten wurden dazu zusammen mit unterschiedlichen Konzentrationen von G-CSF und Ofloxacin inkubiert. Die minimale Hemmkonzentration und sogar ein Viertel der minimalen Hemmkonzentration von Ofloxacin verstärkten die bakterizide Aktivität, 6.000 Einheiten/ml G-CSF führten zu einer signifikanten Verbesserung der bakteriziden Wirkung der neutrophilen Granulozyten. Die Kombination von 6.000 Einheiten/ml von G-CSF mit Ofloxacin in inhibitorischen und subinhibitorischen Konzentrationen zeigten einen synergistischen Effekt während der gesamten Inkubationszeit auf neutrophile Granulozyten. Die Gabe von G-CSF in Kombination mit Antibiotika könnte daher bei Infektionen, insbesondere bei immunsupprimierten Patienten, vorteilhaft sein.Thein vitro effect of subinhibitory and inhibitory concentrations of ofloxacin and G-CSF on the bactericidal activity of polymorphonuclear leucocytes (PMNL) againstEscherichia coli was investigated. PMNL obtained from healthy volunteers were incubated with different concentrations of G-CSF and ofloxacin for 180 min. The minimum inhibitory concentration (MIC) of ofloxacin and even 1/4 × MIC enhanced the bactericidal activity of PMNL. G-CSF at a concentration of 6,000 units/ml led to a significant improvement of the bactericidal activity of PMNL. The combination of 6,000 units/ml of G-CSF and ofloxacin in inhibitory as well as subinhibitory concentrations, however, showed a significant synergistic effect on the antibacterial activity of PMNL during the complete incubation period. Combinations of G-CSF and antibiotics could therefore be beneficial for infected patients, especially those with impaired cellular host defense. Wir untersuchtenin vitro die bakterizide Wirkung von neutrophilen Granulozyten in Kombination mit subinhibitorischen und inhibitorischen Konzentrationen von Ofloxacin und G-CSF aufEscherichia coli. Neutrophile Granulozyten wurden dazu zusammen mit unterschiedlichen Konzentrationen von G-CSF und Ofloxacin inkubiert. Die minimale Hemmkonzentration und sogar ein Viertel der minimalen Hemmkonzentration von Ofloxacin verstärkten die bakterizide Aktivität, 6.000 Einheiten/ml G-CSF führten zu einer signifikanten Verbesserung der bakteriziden Wirkung der neutrophilen Granulozyten. Die Kombination von 6.000 Einheiten/ml von G-CSF mit Ofloxacin in inhibitorischen und subinhibitorischen Konzentrationen zeigten einen synergistischen Effekt während der gesamten Inkubationszeit auf neutrophile Granulozyten. Die Gabe von G-CSF in Kombination mit Antibiotika könnte daher bei Infektionen, insbesondere bei immunsupprimierten Patienten, vorteilhaft sein.

Broad spectrum antibacterial activity of a mixture of isothiocyanates from nasturtium (Tropaeoli majoris herba) and horseradish (Armoraciae rusticanae radix).

Isothiocyanates have been reported to exert antimicrobial activity. These compounds are found in a licensed native preparation of nasturtium (Tropaeoli majoris herba) and horseradish (Armoraciae rusticanae radix) which is used for treatment of upper respiratory and urinary tract infections. The aim of our investigation was to assess the antimicrobial activity of a mixture of the contained benzyl-, allyl-, and phenylethyl- isothiocyanates against clinically important bacterial and fungal pathogens including antimicrobial resistant isolates. Susceptibility testing was performed by agar-dilution technique. Isothiocyanates were mixed in proportions identical to the licensed drug. Minimum inhibitory- and minimum bactericidal concentrations were assessed. The Minimum inhibitory concentration90 was defined as the concentration which inhibited 90% of the microbial species tested. H. influenzae, M. catarrhalis, S. marcescens, P. vulgaris, and Candida spp. were found to be highly susceptible, with minimum inhibitory concentration90 -values ranging between ≤0.0005% and 0.004% (v/v) of total ITC. Intermediate susceptibilities were observed for S. aureus, S. pyogenes, S. pneumoniae, K. pneumoniae, E. coli and P. aeruginosa, with Minimum inhibitory concentration90 -values ranging between 0.004% and 0.125% (v/v), but with elevated Minimum bactericidal concentrations90-values (2-7 dilution steps above Minimum inhibitory concentration90). Low susceptibilities were determined for viridans streptococci and enterococci. Interestingly, both resistant and non-resistant bacteria were similarly susceptible to the test preparation.

MIC and serum bactericidal activity of clindamycin against methicillin-resistant and -sensitive staphylococci.

SummarySix volunteers were given 600 mg clindamycin intravenously to investigate the serum bactericidal activity (SBA) against 50 methicillin susceptible (MSSA) and 50 methicillin resistantStaphylococcus aureus (MRSA) strains. Minimal inhibitory concentrations (MIC) against MSSA, MRSA and 50 methicillin resistant strains ofStaphylococcus epidermidis (MRSE), of which 50% were slime-producing, were determined. SBA of clindamycin against MSSA and MRSA was equally high (mean reciprocal SBA titer against MSSAvs MRSA 1h after application was 13.0vs 13.45), although MICs against MRSA were markedly higher than against MSSA (MIC 90 of MRSAvs MSSA: 0.06vs>32 mg/l). There was no difference in MICs between slime- and non-slime-producing MRSE.ZusammenfassungIn dieser Studie wurde dieIn-vivo-Aktivität von Clindamycin gegen 50 Oxacillin-sensible (MSSA) und 50 Oxacillin-resistenteStaphylococcus aureus(MRSA-)Stämme mit dem Serumbakterizidie-Test/(SBA) untersucht. Sechs Probanden wurde einmalig 600 mg Clindamycin intravenös infundiert. Weiterhin wurde die minimale Hemmkonzentration (MHK) von Clindamycin gegen 50 Oxacillin-sensible und -resistenteS. aureus und 50 Oxacillin-resistenteStaphylococcus epidermidis-Stämme, von welchen die Hälfte Schleim produzierten, bestimmt. Clindamycin hatte eine gleich hohe Serumbakterizidie gegen Oxacillin-sensible und-resistenteS. aureus-Stämme (durchschnittlicher reziproker SBA Titer von MSSAvs MRSA 1h nach Applikation: 13,0vs 13,45), obwohl die MHK-Werte gegen die Oxacillin-sensiblenS. aureus deutlich geringer waren (MHK 90 von MSSAvs MRSA: 0,06vs 32 mg/l). Die MHK-Werte gegen die Oxacillin-resistentenS. epidermidis-Stämme waren ebenfalls niedrig, ein Unterschied zwischen Schleim-, beziehungsweise nicht schleimproduzierenden Stämmen bestand nicht.