The bactericidal activity of vancomycin and teicoplanin against methicillin-resistant strains of coagulase negative Staphylococcus spp.
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Coagulase↗
Biomedical subjects
D Felmingham
Publications and source records attributed to D Felmingham.
In vitro activity and synergy studies with fleroxacin.
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Anti-Bacterial Agents↗
In vitro bactericidal activity of the glycopeptide compounds vancomycin, teicoplanin and ramoplanin (A-16686/MDL 62,198).
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Anti-Bacterial Agents↗
Resistance studies with ofloxacin.
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Drug Resistance, Bacterial↗
Comparative in vitro activity of ciprofloxacin and other unrelated antimicrobials against bacterial respiratory tract pathogens.
Ciprofloxacin is a new fluorinated 4-quinolone with a broad spectrum of antimicrobial activity which includes both Gram-negative and Gram-positive bacteria. In this study the in vitro activity of ciprofloxacin has been determined against bacteria associated with respiratory tract infections and compared with that of other antimicrobial agents used in the therapy of such infections. Ciprofloxacin (MIC90 0.008 mg/l) was highly active against Haemophilus influenzae, including isolates producing beta-lactamase which were resistant to amoxycillin. Ciprofloxacin (MIC90 0.06 mg/l) was also highly active against Branhamella catarrhalis, again including those isolates resistant to amoxycillin as a result of beta-lactamase production. Isolates of Streptococcus pneumoniae were less susceptible to ciprofloxacin (MIC90 2 mg/l) but were highly susceptible to amoxycillin (MIC90 less than 0.12 mg/l) and erythromycin (MIC90 0.25 mg/l). Isolates of Klebsiella aerogenes were highly susceptible to ciprofloxacin (MIC90 0.06 mg/l) but much less so to amoxycillin, sulfamethoxazole, trimethoprim, oxytetracycline and erythromycin. Ciprofloxacin (MIC90 0.5 mg/l) was very active against Staphylococcus aureus, including those isolates resistant to amoxycillin and flucloxacillin, and against Mycoplasma pneumoniae. Together with rifampicin and erythromycin, ciprofloxacin was highly active against Legionella pneumophila (MIC90 0.015 mg/l). These results suggest that clinical evaluation of ciprofloxacin in the treatment of respiratory tract infections is justified.
Anti-Bacterial Agents↗
In vitro activity of dactimicin and other aminoglycosides against bacteria producing aminoglycoside-modifying enzymes.
Dactimicin is a new pseudo-disaccharide aminoglycoside, originally isolated from cultures of Dactylosporangium matsuzakienzae sp. nov., which is chemically related to astromicin. In this study the in vitro activity of dactimicin has been determined against strains of bacteria producing characterized aminoglycoside-modifying enzymes and has been compared with that of gentamicin, tobramycin, netilmicin and amikacin. Minimum inhibitory concentrations were determined using an agar incorporation technique in Mueller-Hinton agar with an inoculum of approximately 10(4) cfu. Dactimicin was resistant to inactivation by a number of different acetyltransferases (AAC), produced by species of the Enterobacteriaceae, most of which inactivated gentamicin, tobramycin and netilmicin. The exception was an AAC(3')-I produced by an isolate of Escherichia coli, which inactivated gentamicin and dactimicin but not tobramycin, netilmicin and amikacin. Dactimicin was inactivated by the adenyltransferases (AAD) AAD(2") and AAD(9), produced by Pseudomonas aeruginosa, but not by an AAD(4')(4"), produced by a strain of Staphylococcus aureus, nor by an AAD(2") produced by a strain of E. coli. Dactimicin was inactivated by a combination of a phosphotransferase (APH) APH(2") and an AAC(6') produced by strains of S. aureus. The results suggest that dactimicin may retain useful antibacterial activity against many gentamicin-resistant strains of bacteria belonging to the Enterobacteriaceae and some gentamicin-resistant strains of S. aureus.
Acetyltransferases↗
In vitro activity of sulphamethoxazole/trimethoprim and sulfadoxine/pyrimethamine against Chlamydia trachomatis SA2f in McCoy cell culture.
Chequerboard titrations of sulphamethoxazole/trimethoprim and sulfadoxine/pyrimethamine were performed against Chlamydia trachomatis (strain SA2f) using McCoy cell monolayers in vials. The experiments were continued for ten passages each. The mean fractional inhibitory concentration index for each combination was calculated. Results demonstrated synergistic activity between sulphamethoxazole and trimethoprim, and between sulfadoxine and pyrimethamine.
Cell Line↗
Contamination of blood during cardiopulmonary bypass: the effect of antibiotic prophylaxis.
Despite antibiotic prophylaxis in cardiac surgery, gram-positive bacteria can be isolated in up to 10% of intraoperative blood cultures. During a prospective randomized trial, blood was collected from the oxygenator at the end of bypass in 58 patients given teicoplanin and in 60 others given flucloxacillin and tobramycin. Coagulase-negative staphylococci were cultured from 16 patients given teicoplanin but in only four cases after flucloxacillin and tobramycin (Fisher's exact test, P = 0.005). In contrast, Propionibacterium spp. or coryneforms were isolated from 22 patients given flucloxacillin and tobramycin and from only one patient in the teicoplanin group. There were no cases of prosthetic valve endocarditis. After 3 h exposure to 4 x MIC of teicoplanin there was only a 10-60 fold reduction in cfus of Staphylococcus epidermidis, which may partly explain the excess of these organisms.
Anti-Bacterial Agents↗
Susceptibility of Pseudomonas pseudomallei to new beta-lactam and aminoglycoside antibiotics.
Pseudomonas pseudomallei is resistant to many antimicrobial agents. We determined the susceptibility to twelve beta-lactams and six aminoglycosides of twelve isolates of P. pseudomallei. Imipenem (MIC range 0.5-1.0 mg/l; MIC90 1.0 mg/l), ceftazidime (MIC range 1-8 mg/l; MIC90 8.0 mg/l), amoxycillin/clavulanate (MIC range 4-8 mg/l; MIC90 8.0 mg/l), piperacillin (MIC range 4-16 mg/l; MIC90 8.0 mg/l), and carumonam (MIC range 4-16 mg/l; MIC90 8.0 mg/l) were the most active. Aminoglycosides were relatively inactive, for example, gentamicin (MIC range 16-64 mg/l; MIC90 64 mg/l), netilmicin (MIC range 16-128 mg/l; MIC90 128 mg/l) and amikacin (MIC range 32-64 mg/l; MIC90 64 mg/l).
Aminoglycosides↗
Antibiotic prophylaxis in cardiac surgery: serum and tissue levels of teicoplanin, flucloxacillin and tobramycin.
In this study, the pharmacokinetics of teicoplanin have been studied in serum, fat and bone during and after cardiac surgery with two dose (400 and 200 mg) and three dose (400 mg each) regimens in a total of 49 patients. For comparison, 20 other patients, who had received a regimen of flucloxacillin (500 mg qds for five days) and tobramycin (1.5 mg/kg initially then 80 mg tds for three days), were similarly investigated. The lowest mean serum level of teicoplanin during operation was 6.9 mg/l in the two dose regimen and 9.7 mg/l with the three dose regimen. Mean serum levels of flucloxacillin and tobramycin fell to 7 and 1.4 mg/l respectively by the end of operation. At the end of bypass, fat washings contained a mean of 1.2 mg/l of teicoplanin and bone washings a mean of 6.3 mg/l. Mean tobramycin levels were 0.4 and 0.9 mg/l respectively and flucloxacillin less than 1 mg/l in washings from both tissues. The low levels of teicoplanin in fat may explain an excess of Gram-positive sternal infections in the accompanying clinical trial.
Anti-Bacterial Agents↗
Resistance studies with ofloxacin.
The selection of ofloxacin-resistant mutants from susceptible wild-type bacterial populations was investigated by three methods. Resistant mutants selected from populations of Escherichia coli (NCTC 10418) and Staphylococcus aureus (NCTC 6571) by single-step passage at either four or eight times the MIC occurred at a frequency of less than 1 x 10(-10). Ofloxacin-resistant mutants of Pseudomonas aeruginosa (NCTC 10662), selected at four times the MIC, occurred with a 100-fold greater frequency at 3.3 X 10(-8), however, mutants of this species selected at eight times the MIC, occurred at a frequency of less than 1 X 10(-10). Sequential selection of ofloxacin-resistant mutants during multiple passages at 1/2 MIC, resulted in a 16- to 32-fold increase in MICs for isolates of P. aeruginosa and Klebsiella aerogenes, a four- to eight-fold increase in MICs for some strains of E. coli and a two- to four-fold increase in MICs for Staph. aureus and Streptococcus spp. During prolonged exposure of populations of E. coli (NCTC 10418) and Staph. aureus (NCTC 6571) to concentrations of ofloxacin at 1, 10 and 100 times the MIC no resistant-mutants were selected after seven days incubation. In similar experiments with P. aeruginosa (NCTC 10662) ofloxacin-resistant mutants were selected from populations exposed to the MIC which required 64 mg/l ofloxacin for inhibition. No ofloxacin-resistant mutants were selected from populations of P. aeruginosa (NCTC 10662) exposed to either ten or 100 times the MIC.(ABSTRACT TRUNCATED AT 250 WORDS)
Drug Resistance, Microbial↗
The comparative in-vitro activity of ofloxacin.
The antibacterial activity of ofloxacin, a new fluoroquinolone, was evaluated against a wide range of clinical bacterial isolates and compared with that of nalidixic acid, norfloxacin, enoxacin, pefloxacin and ciprofloxacin by determination of minimum inhibitory concentrations (MICs). Ofloxacin was very active against nalidixic acid-susceptible isolates of the Enterobacteriaceae (MIC less than or equal to 0.12 mg/l) and was also active against strains resistant to nalidixic acid (MIC less than or equal to 2 mg/l). The activity was similar to norfloxacin, enoxacin and pefloxacin but some four-fold less than that of ciprofloxacin. All of the fluoroquinolones were highly active against Vibrio cholerae (MIC less than or equal to 0.015 mg/l), V. parahaemolyticus (MIC less than or equal to 0.12 mg/l) Aeromonas hydrophila (MIC less than or equal to 0.03 mg/l), Plesiomonas shigelloides (MIC less than or equal to 0.015 mg/l), Campylobacter jejuni (MIC less than or equal to 0.5 mg/l), Neisseria spp., Haemophilus influenzae, H. ducreyi, Bordetella pertussis and Legionella pneumophila (MIC less than or equal to 0.06 mg/l for all species). Ofloxacin, ciprofloxacin and pefloxacin (MIC less than or equal to 1, 2 and 2 mg/l, respectively) showed similar activity against Staphylococcus spp. and were somewhat more active than enoxacin (MIC less than or equal to 4 mg/l) and norfloxacin (MIC less than or equal to 8 mg/l). Ofloxacin was moderately active against beta-haemolytic Streptococcus spp. (MIC less than or equal to 2 mg/l), Corynebacterium diphtheriae (MIC less than or equal to 1 mg/l) and Cory. jeikeium (MIC less than or equal to 2 mg/l) and somewhat less active against alpha- and non-haemolytic Streptococcus spp., Str. pneumoniae and Listeria monocytogenes (MIC less than or equal to 4 mg/l for all species) and Str. faecalis (MIC less than or equal to 8 mg/l). The activity of ofloxacin, against these species, was similar to ciprofloxacin and four to eight times greater than norfloxacin, enoxacin and pefloxacin. Ofloxacin, and all of the fluoroquinolones, were less active against anaerobic than aerobic bacteria. Clostridium perfringens (MIC less than or equal to 1 mg/l) was more susceptible to ofloxacin than were other anaerobic species and Cl. difficile (MIC less than or equal to 16 mg/l) was more resistant. Ofloxacin was the most active compound tested against Chlamydia trachomatis SA2f (MIC less than or equal to 0.5 mg/l) with only ciprofloxacin (MIC less than or equal to 1 mg/l) approaching similar activity.(ABSTRACT TRUNCATED AT 400 WORDS)
Bacteria, Anaerobic↗
In vitro activity of azithromycin (CP-62,993), a novel macrolide, against enteric pathogens.
Azithromycin (CP-62,993 [9-deoxy-9A-methyl-9A-aza-9A-homoerythromycin]) is a novel macrolide antimicrobial. In this study the in vitro activity of CP-62,993 has been determined against selected enteropathogens, including Clostridium difficile, and compared with that of erythromycin. MICs were determined using an agar incorporation technique in Mueller-Hinton medium, containing saponin-lysed horse blood at a final concentration of 10% v/v, with an inoculum of 10(4) cfu. CP-62,993 was considerably more active than erythromycin against Salmonella typhi (MIC90 4 and greater than 32 mg/l, respectively), S. enteritidis (MIC90 4 and greater than 32 mg/l), Shigella flexneri (MIC90 2 and 32 mg/l), Sh. dysenteriae (MIC90 2 and 32 mg/l), Sh. sonnei (MIC90 4 and 32 mg/l), Campylobacter jejuni (MIC90 0.12 and 1 mg/l), Vibrio cholerae (MIC90 0.25 and 8 mg/l), V. parahaemolyticus (MIC90 0.5 and 8 mg/l), Yersinia enterocolitica (MIC90 4 and greater than 32 mg/l), Escherichia coli-ETEC (MIC90 4 and 32 mg/l), E. coli-EIEC (MIC90 4 and greater than 32 mg/l), Plesiomonas shigelloides (MIC90 1 and 8 mg/l) and Aeromonas hydrophila (MIC90 4 and 32 mg/l). CP-62,993 (MIC90 2 mg/l) was slightly less active than erythromycin (MIC90 1 mg/l) against isolates of C. difficile. The results suggest a potential clinical role for CP-62,993 in the treatment of enteric infections where antimicrobial therapy is indicated.
Azithromycin↗
The in vitro activity of ramoplanin (A-16686/MDL 62,198), vancomycin and teicoplanin against methicillin-susceptible and methicillin-resistant Staphylococcus spp.
Ramoplanin (A-16686/MDL 62,198) is a novel lipoglycopeptide antimicrobial, comprised of three closely related polypeptides containing chlorinated phenyl moieties and D-mannose, isolated from the fermentation products of Actinoplanes sp. ATCC 33076. The antimicrobial activity of ramoplanin is limited to Gram-positive bacteria and its reportedly unacceptable administration side-effects suggest that any potential clinical role will be limited to the topical therapy of superficial skin infections and the eradication of bacteria, representing a possible nosocomial cross-infection source, from carriage sites. In this study the MICs of ramoplanin have been determined for methicillin-susceptible and methicillin-resistant isolates of Staphylococcus aureus, S. epidermidis and S. haemolyticus and compared with those of two glycopeptide antimicrobials, vancomycin and teicoplanin. MICs were determined using an agar incorporation technique in Mueller-Hinton medium with an inoculum of 10(5) cfu. Ramoplanin was 2-8 times more active than either vancomycin or teicoplanin against methicillin-susceptible and methicillin-resistant isolates of S. aureus and methicillin-susceptible isolates of S. epidermidis. Isolates of methicillin-resistant S. epidermidis and both methicillin-susceptible and -resistant isolates of S. haemolyticus were generally less susceptible to teicoplanin than to vancomycin. Ramoplanin was significantly more active than either vancomycin or teicoplanin against these isolates. These results suggest that the clinical evaluation of ramoplanin as a topical antibacterial agent for the control of superficial infections caused by Staphylococcus spp. and for the eradication of methicillin-resistant S. aureus from carriage sites, is justified.
Anti-Bacterial Agents↗
A high performance liquid chromatography method for the determination of FCE 22101, a novel penem antimicrobial, in serum.
FCE 22101 (sodium [5R, 6S, 8R]-6-alpha-hydroxyethyl-2-carbamoyloxymethyl-2- penem-3-carboxylate) is a new penem antimicrobial with a broad spectrum of activity. In order to investigate the pharmacokinetics of FCE 22101 in human volunteers, a high performance liquid chromatographic assay has been developed for determining concentrations of FCE 22101 in serum. Serum samples were deproteinised with an equal volume of acetonitrile followed by centrifugation. The supernatant was then diluted with an equal volume of 0.05 M phosphate buffer (pH 7.0) and 50 microliters was applied to the separation column. Chromatographic separation of FCE 22101 was achieved using an SP8700 solvent delivery system (Spectra-Physics), an SP8780XR autosampler (Spectra-Physics) and a reverse-phase C18 mu-BondaPak column (8 X 100 mm) radially compressed in a Z module (Millipore, UK). The mobile phase consisted of a water, methanol and orthophosphoric acid mixture (74:25:1), which was filtered through a 0.22 micron filter and de-gassed under vacuum prior to use. The flow rate was 1.4 ml/min and FCE 22101 was detected in the column eluant using an LC871 UV-Vis detector set at 318 nm. The data were analysed using an SP4270 integrator (Spectra-Physics). The lower limit of sensitivity of the assay method was 0.8 mg/l and recovery from deproteinised serum was of the order of 70%. Intra-assay variation was less than 5% and inter-assay variation was less than 10%.
Anti-Bacterial Agents↗
Activity of sodium fusidate in vitro against anaerobic bacteria.
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Bacteria, Anaerobic↗
The in-vitro activity of doxycycline and minocycline against anaerobic bacteria.
The likelihood of bacterial resistance now prevents the use of oxytetracycline in the empirical therapy of anaerobic infections. This study investigates the in-vitro activity of two semi-synthetic derivatives, doxycycline and minocycline, against a range of anaerobic bacteria. MICs for each antibiotic were determined by an agar incorporation technique. Doxycycline and minocycline were four to eight times more active against the majority of strains than oxytetracycline. With the exception of Bacteroides bivius, almost 90% of strains were inhibited by 4 mg/l of doxycycline or minocycline, but resistance to the same concentration of oxytetracycline was present in 60% of the B. fragilis group, 30% of Peptostreptococcus spp. and 24% of Clostridium perfringens. Doxycycline and minocycline represent an alternative therapy for anaerobic infections where bacterial sensitivities are known.
Bacteria, Anaerobic↗
The effect of medium and inoculum on the activity of vancomycin and teicoplanin against coagulase-negative staphylococci.
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Anti-Bacterial Agents↗